Multiple roles of a histaminergk afferent neuron in the feeding behavior of Aplysia Hillel J. C h i e l , K l a u d i u s z R. W e i s s a n d I r v i n g K u p f e r m a n n
The cellular and circuit properties of individual identified neurons in invertebrates can be readily studie& hence it is possible to determine how the complex properties of nerve ceils function in the generation of behavior. Recent studies of the cellular basis of feeding behavior in the marine mollusc Aplysia have focused on a neuron, C2, that has a variety of complex properties that determine the behavioral functions of the neuron. C2 conveys mechanosensory information from the mouth of the animal. It receives a complex pattern of inputs during feeding behavior, and generates diverse outputs that may shape behavior. It can act to filter out slow or sporadic sensory inputs, and its own outputs can be 'gated' by synaptic input. C2 uses histamine as its transmitter, and some of its synaptic outputs are modulatory and contribute to the expression of an arousal state induced by food. Other outputs shape feeding behavior directly by affecting motor neurons, as well as presynaptically inhibiting the outputs of feeding motor programs. Thus, the complex properties of this neuron may contribute to the flexibility and adaptability of feeding in Aplysia. Studies of C2 have expanded our concepts of the properties of sensory neurons. The complex properties of individual nerve cells contribute significantly to the information processing capacity of the nervous system. Invertebrates offer an opportunity to relate cellular properties and knowledge of connections to behavior and function. An example of this is provided by studies of an identified histaminergic neuron, C2, located in the cerebral ganglion of Aplysia. The biochemistry, pharmacology, electrophysiology, morphology and behavioral role of C2 have been studied extensively. Firing of C2 evokes a wide variety of synaptic responses in various neurons in the cerebral ganglion. These responses include fast excitation, fast inhibition, slow excitation, slow inhibition, and very slow excitation L2. Over the past 15 years, due primarily to the work of McCaman, Weinreich, Ono and their collaborators 3~9, a substantial amount of evidence has been accumulated which indicates that the various synaptic responses of C2 are mediated by the release of histamine from the neuron.
C2 receives complex excitatory and inhibitory inputs during feeding behavior When food (seaweed) stimuli are presented to the lips of the animal, C2 exhibits a burst of excitatory potentials that summate and produce action potentials in its soma. If the food is maintained on the lips, rhythmic feeding movements occur. During this behavior, C2 receives bursts of excitatory and inhibitory potentials in phase with each movement (Fig. 1) 1°. The activity of C2 is shaped by the inhibitory output of feeding motor programs The inhibitory synaptic potentials received by C2 are produced by the activity of two interneurons TINS, Vol. 13, No. 6, 1990
(B17 and B18) that are located in the buccal ganglion1]. B18 provides outputs to many cerebral cells other than C2, some of which are involved in controlling movements of the lips and tentacles of the animal11. Thus, B18, and other buccal neurons like it, may serve to 'read out' the feeding motor program onto neurons controlling muscles that must be coordinated with those of the main feeding apparatus. (See below for a discussion of the possible functional significance of these inhibitory inputs.)
C2 is a mechanoafferent and proprioceptor Every time the jaws close during the feeding program, the soma of C2 exhibits excitatory potentials 1°. These excitatory potentials have the appearance and functional properties of synaptic potentials (see below), but they are not synaptic potentials; rather, they are blocked axon spikes (A spikes). Mechanosensory information from the periphery is conveyed centrally to the soma of C2 through its peripheral axons innervating the mouth region. Action potentials in the peripheral nerves often fail to invade the soma and initial axon of C2, and are propagated passively to the soma 12.
HillelJ. Chielisat the Departmentof Biology,Case WesternReserve University,2080 AdelbertRoad, Cleveland,OH 44106, USA. KlaudiuszR. Weiss andIrving Kupfermannare at the Centerfor Neurobiologyand Behavior,New York StatePsychiatric InstituteandCollege of Physiciansand Surgeonsof Columbia University,722 West 168thStreet,New York,NY 10032, USA.
C2 can integrate, filter and gate sensory input C2 has an unusual morphology (Fig. 2). Emanating from the cell body is a very stout process that has extensive invaginations 1~,1~. The stout initial process gives off numerous fine processes that provide the synaptic output of the cell to numerous follower cells in the cerebral ganglion. More distally, the initial
MCC r
IIJJ L L Buccal mass -'-"-" pressure
--
t I
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I I
II
fl
tl
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Fig. 1. Intracellular recordings from C2 and the metacerebral cell (MCC),
during rhythmic biting responses. The records were obtained from a 'semiintact' preparation consisting of the isolated head and the exposed cerebral ganglion. Movements of the buccal mass (the organ that grasps and swallows food) are indicated by recording the associated alterations in blood pressure as the organ moves forwards (up arrow) and backwards (down arrow). Application of a food stimulus (seaweed) results in an initial activation of C2 and the MCC, followed by rhythmic bursts of depolarizing and hyperpolarizing potentials in C2, which occur in phase with each buccal movement. The phasic activity persists for a period of time after the food is removed. (Taken, with permission, from Ref. 10.)
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process trifurcates to form very fine peripheral axons that innervate the area around the mouth. These Pattern morphological features appear to allow C2 to function generator as a gate for peripheral mechanosensory information. The gating function takes two forms. First, the cell acts as a high pass filter that permits only relatively strong and prolonged mechanostimuli to produce any synaptic outputs from the cell. Second, inhibitory synaptic input to the cell can override and 'gate out' C2 even strong stimulation. The gating properties of C2 are dependent on the fact that the cell produces synaptic output only if its peripheral axonal spikes produce full action potentials in the thick initial segment of the cell, and thereby invade the synaptic terminal region (see fight-hand traces of Fig. 2) 12. However, the initial segment of C2 is a region of low safety factor, which can cause incoming A spikes to fail (see initial potentials of the 'initial segment' trace in Fig. 2). As a consequence, the A spikes in C2 exhibit temporal and spatial summation. The cell is normally in an 'off' state and completely filters out low-intensity stimulation. The frequency and duration of firing of the peripheral axon determines whether successive A spikes will summate sufficiently to depolarize the initial segment to a level that triggers action potentials. Furthermore, A spikes from the three peripheral axons of the cell exhibit spatial summation, which also acts to overcome the blockage. The action potential in the soma and the initial process of C2 exhibit a depolarizing afterpotential; thus, once the cell is brought to threshold, subsequent A spikes ride on a depolarization, so that they more readily elicit spikes. Finally, Mouth the A spikes show a form of short-term plasticity facilitation. As the initial segment depolarizes, and the region of failure moves closer to the soma of C2, the incoming A spikes increase in size (see initial potentials of the 'initial segment' trace in Fig. 2) 12. Thus, the unique morphology of C2 causes its electrotonic inputs to manifest properties that are usually associated with chemical synaptic inputs - spatial and Fig. 2. Schematic representation of C2 and selected cells in the cerebral ganglion with which it is interconnected. The relative length of the peripheral temporal summation, and facilitation. The integrative properties of C2 also account for its axons of C2 are much longer than indicated. The figure illustrates the types of intracellular recordings that can be obtained when the mouth spontaneously sensitivity to inhibitory inputs, which may gate it on or closes or is briefly contacted with a tactile stimulus. The panels on the right off. C2 receives inhibitory synaptic input, which can illustrate hypothetical simultaneous recordings from the axon and initial significantly reduce the summation of incoming A segment of C2 (lower two panels), and from examples of two 'follower' cells of spikes, primarily by increasing the conductance of the C2 (upper two panels). The lower right panel shows that a tactile stimulus cell and enhancing the rate of decay of the A spikes. (indicated by the bar) evokes action potentials, which can be recorded in the This serves to prevent them from inducing full spikes peripheral axon of (52. The record labeled 'initial segment' illustrates that when in C2 (Ref. 12). Thus, the inhibitory synaptic input to the first spikes reach the region of the initial segment, they fail to trigger full the cell can serve to turn off the synaptic output of the spikes and appear as facilitating axon spikes (A spikes) that are electrotonically transmitted from some region in the axon (probably relatively close to the cell completely, even when the peripheral axons fire initial segment) at which spikes fail. Thus, low-frequency inputs will tend to be at moderately high rates. In fact, C2 receives two filtered out by C2. If the A spikes occur at a sufficiently high frequency, they types of inhibitory potential - a fast, discrete IPSP and summate, and in this example they reach threshold and evoke six full spikes. a more prolonged, slow IPSP 1°. The fast IPSP The upper two records illustrate that C2 can produce slow synaptic potentials inactivates C2 during a specific phase of the bite cycle, (e.g. in neuron C4 and the AACC), as well as fast synaptic potentials (e.g. in and may affect the ability of C2 to shape motor motor neuron C6), and that the synaptic output of C2 only occurs when a full outputs during feeding. In contrast, the slow IPSP spike appears in the initial segment. The diagram also shows that C2 receives may act to block the response of C2 to food-related inhibitory synaptic input from 'corollary discharge' units that are located in the stimuli completely, and thus to modulate the behavbuccal ganglion. The example given shows neuron B18. B18 can be activated in a phasic fashion by input from the pattern-generating neurons that ioral state of the animal. determine the phasing of buccal muscle contraction. The neuron also receives excitatory input from the gut. B18 inhibits C2, and excites other cerebral C2 excites an 'executor' of the feeding arousal ganglion neurons (e.g. C4). C2 probably makes presynaptic connections (filled s y s t e m C2 contributes to the arousal of feeding behavior by circles connected to C2) with the terminals of B18 and other buccal interneurons, producing presynaptic inhibition. (Based on data from Refs 11, providing slow excitatory input to the metacerebral 12 and 20.) cell (MCC), an identified serotonergic neuron that
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serves as an 'executor' of certain aspects of foodinduced arousal. The MCC acts at a variety of loci to affect feeding behavior: it can increase the activity of the central pattern generator for feeding, it provides slow excitation to feeding motor neurons, and it acts directly on muscles involved in feeding to enhance their contraction in response to excitation from motor neurons 14-16. The MCC fires when animals are exposed to food15, and its activity is enhanced by the slow, monosynaptic excitatory input from C2 (Ref. 17). The connection from C2 to the MCC has several properties appropriate for a modulatory role. The EPSP is associated with a voltage-dependent decrease of the conductance of the MCC (C2 produces a similar EPSP in C4; see Fig. 2). The EPSP becomes much larger when the MCC is depolarized. The decreased conductance also increases the effectiveness of any incoming depolarizing currents. Finally, the excitatory effect of C2 decays very slowly so that it can continue to sum over many seconds 17. Thus, even if C2 fires phasically, its primary effect on the MCC will be to increase the level of activation of the cell tonically.
C2 may act to maintain feeding arousal C2 is activated by tactile stimuli to the lips, but once the feeding motor program is active, even in the absence of food stimuli, proprioceptive inputs from the lips and jaws excite C2 during each feeding movement. Excitation of C2 increases the firing of the MCC, and the MCC activity increases the rate of the motor program output 1°. Thus, a positive feedback loop is established: feeding movements excite C2, which in turn excites the MCC, which then enhances the feeding movements that re-excite C2. Since inhibition of C2 could act to break the positive feedback loop of which it is a part, and thus decrease the food arousal of the animal, such inhibition could serve effectively to reduce arousal of the consummatory phase of feeding behavior. In fact, a neuron in the buccal ganglion, B18, monosynaptically inhibits C2 by means of a dual, fast and slow IPSP TM. As mentioned above, B18 receives phasic excitation from pattern-generating neurons during the feeding motor program. In addition, B18 is excited by stimulation of the esophageal nerve or by dilation of the gut TM. During feeding behavior in Aplysia, sensory inputs indicating that the gut has dilated may serve as a satiety signal and reduce the intensity of feeding19. C2 shapes the output of feeding musculature The synaptic actions of C2 on the MCC suggested that it was primarily responsible for slow, modulatory actions. However, its other synaptic outputs suggested that C2 might act on a more rapid time scale to shape the output of feeding motor programs. The phasic inhibition that C2 receives during each bite might then serve to sharpen the shaping function of C2, by permitting sensory information to affect follower cells only during a specific phase of the movement. Several of the neurons that receive fast, phasic synaptic input from C2 act to modulate feeding behavior. These neurons are excitatory or inhibitory motor neurons for muscles of the lips or the body wall of the head, and for muscles that connect the buccal mass to the body wall (the extrinsic muscles of the TINS, Vol. 13, No. 6, 1990
6 x Ca 2+, 3 X Mg 2+
04llillllllllH!llllllll l lll II llllllillillll,
III [!llll[lllllllIll[[ll[[[[[lllllll[lIllll,
.....................................lllt....................................
c2 ~
~
'
~
~ .._j 5mY (C4) 20mY (B18) 5s
Fig. 3. C2 reduces the size of the EPSPin C4 evoked by firing B18. Each EPSPin C4 was evoked by triggering a single spike in B18. Note that the gain of the top record is four times that of the lower records, and that the slow sweep speed makes the EPSPsin C4 appear spike-fike. (Taken, with permission, from Ref. 11 .)
buccal mass) 2°. When C2 is fired experimentally at rates that a r e comparable to those at which it fires during feeding, it can exert effects on the feeding musculature through its synaptic followers. Extracellnlar recordings from these muscles during feeding behavior indicate that they contract in phase with the firing of C2 (Ref. 20). Thus, the phasic activation of C2 that occurs during feeding may affect the activity of feeding musculature. The muscles upon which C2 acts do not appear to be necessary for the execution of feeding responses, but instead modulate the efficiency of feeding. Removal of these muscles does not prevent animals from eating, but the amount of seaweed they ingest with each swallow is reduced 2°. Thus, these muscles appear to serve a platform or postural role, against which other muscles that mediate feeding can act to generate movements, enhancing feeding efficiency.
C2 presynaptically inhibits outputs from feeding motor p r o g r a m s While feeding motor programs shape the synaptic output of C2, the cell can reciprocally inhibit the outputs of feeding motor programs. When C2 is fired at rates observed in the semi-intact preparation, it can reduce or eliminate the phasic synaptic inputs that impinge on it and on its followers. The ability of C2 to do this is, in large part, a consequence of its actions on buccal neuron B18, whose synaptic effects on C2 and its follower cells are reduced when C2 fires (Fig. 3) 11. C2 is likely to exert at least part of its inhibitory effect directly on the presynaptic terminals of B18, because C2 reduces the synaptic output of B18 when both the cerebral and buccal ganglia are bathed in a solution that reduces or eliminates polysynaptic pathways (high divalent cation solution); also, quantal analysis (variance analysis) of the effects of C2 on the connection between B18 and cerebral neuron C4 indicates that C2 acts to reduce the number of quanta released by B18. Since histamine strongly hyperpolarizes the soma of B18, a similar action on the 225
terminals of B18 might explain the observed presynaptic action of C2 (Ref. 11). What is the physiological function of the reciprocal inhibition between C2 and buccal neuron B18? One possibility is that the reciprocal inhibition allows the animal to adapt flexibly to rapid changes in the load on its feeding apparatus that occur when it encounters unexpectedly tough pieces of food. C2 will be strongly activated by such an increased load, and may then strengthen the retraction phase of swallowing (i. e. the phase in which food is pulled into the feeding apparatus) by its actions on motor neurons, and at the same time prolong retraction by its inhibition of elements of the feeding circuitry that control protraction (i.e. the phase in which the feeding apparatus is thrust forward). Indirect evidence for this hypothesis is provided by extracellular recordings from extrinsic buccal muscle E4, whose motor neuron receives excitatory input from C2. When a piece of seaweed that an animal has swallowed is pulled, increasing the load on the feeding apparatus, muscle E4 shows large increases in its excitation, and presumably in the force that it generates 2°. Concluding remarks Studies of C2 have shed further light on the cellular basis of feeding behavior, and have more fully defined the physiological role that histamine plays in a part of the nervous system of Aplysia. The studies reviewed here indicate that C2 uses histamine as its transmitter, and that this transmitter can act rapidly or slowly to excite or inhibit a large number of other neurons in the nervous system of Aplysia. C2 is excited by mechanical stimuli and by movements of the mouth of the animal during feeding. In turn, it excites an 'executor' neuron for the feeding arousal system, the MCC. Since the MCC can further activate feeding movements, C2 may be part of a positive feedback loop that helps maintain arousal. In addition, the unusual morphology of C2 and its intrinsic properties allow it to integrate sensory information from the lips spatially and temporally, and thus serve to filter out weak inputs, while amplifying strong ones. Inhibitory input to C2 can gate it on or off. Since some of the inhibitory inputs that C2 receives are due to stretch of the gut, a signal for satiation, C2 may be part of the process that switches an animal from a state of feeding arousal to satiation. C2 can also act on the motor neurons for a variety of muscles that serve to improve the efficiency of feeding. C2 and feeding motor programs interact through reciprocal inhibition, which is likely to contribute to the adaptive flexibility that Aplysia shows during feeding. On the one hand, the motor program can act to coordinate different muscles during feeding, and suppress the activity of C2 and its followers in the appropriate phase of the behavior. On the other hand, C2 may respond to increases in the load on the feeding apparatus, and act to shape the outputs of the motor program in order to enhance an appropriate motor response to the new situation. It is interesting that recent studies on the feeding system of another invertebrate, the crab, have described cells that share a number of properties with C2 (Ref. 21). The gastropyloric receptor (GPR) cells of the crab are proprioceptors that produce both fast and slow modulatory central actions, and are involved in a 226
positive feedback loop. Another interesting parallel to the studies described here is provided by work on the inferior ventricular nerve (IVN) interneurons in another crustacean, the lobster. These neurons are mechanoreceptors that respond to stretch of the posterior part of the stomach, appear to use histamine as their transmitter, and cause shifts in the motor output of the stomatogastric ganglion through their synaptic connections within it22,23. In general, histamine appears to play complex sensory roles in a variety of different invertebrates 24. The studies of C2 and the organization of feeding behavior in Aplysia may provide more general insights into the organization of complex behavior. First, these studies strengthen the growing evidence that some sensory neurons may play a broader role than is typically assumed 25,26. Rather than faith_fully and rapidly transmitting information from the periphery, they may also preprocess it in complex ways, and act to modulate central circuitry over relatively long periods of time. Second, it is possible that, in part, arousal may be maintained in the absence of extemal sensory inputs by using proprioceptive inputs generated by the animal itself. An animal's own movements may then act to prevent the decay of arousal even when the goal object (e.g. food) becomes unavailable for a period of time. Third, the properties of C2 suggest that arousal systems may not consist of cells whose role is related solely to maintenance or regulation of arousal. Some elements of arousal systems may act both to increase arousal and to subserve a more specific modulatory effect on parts of the motor system that control a particular behavior. Finally, these data suggest one mechanism for generating flexible, adaptive behavior. Motor programs appear to use corollary discharge to coordinate a variety of different muscles during complex behaviors. However, sensors of local conditions at the different parts of the motor system that receive the motor program may suppress and override the basic program. As a consequence, specific parts of the motor system may be capable of independently adjusting their outputs as demands on that part of the system change. Studies of C2 illustrate the importance of considering the complex properties of individual nerve cells. In the past, the complexity of invertebrate nerve cells has been explained as a compensatory mechanism for generating complex behavior with relatively few nerve cells. However, studies of mammalian nerve cells have revealed that they too possess great complexity in their morphology and their conductances 27. Models of neural computation that incorporate these complexities are likely to be harder to analyse, and slower to simulate. However, their benefits may outweigh their costs: it may be easier to relate them directly to neurobiological data, and thus to test them experimentally. Most importantly, they may succeed in doing difficult computations with fewer elements.
Selected references 1 /VkCarnan, R. E. and Weinreich, D. (1985) J. Neurophysiol. 53, 1016-1037 2 0 n o , J. K. and McCaman, R. E. (1985) in Model Neural Networks and Behavior (Selverston, A. I., ecl.), pp. 303-317, Plenum Press 3 Weinreich, D., Weiner, C. and McCaman, R. (1975) Brain
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Res. 84, 341-345 4 Weinreich, D. (1977) Nature 267, 854-856 5 Weinreich, D. and Yu, Y. T. (1977) J. Neurochem. 28, 361-369 6 Weinreich, D. (1978) in Biochemistry of Characterized Neurons (Osborne, N., ed.), pp. 153-175, Pergamon 7 McCaman, R. E. and McKenna, D. G. (1978) Brain Res. 141, 165-171 8 0 n o , J. K. and McCaman, R. E. (1980) Neuroscience 5, 835-840 9 Stein, C. and Weinreich, D. (1982) J. Neurochem. 38, 204-214 10 Weiss, K. R., Chiel, H. J., Koch, U. and Kupfermann, I. (1986) J. Neurosci. 6, 2403-2415 11 Chiel, H. J., Kupfermann, I. and Weiss, K. R. (1988) J. Neurosci. 8, 49-63 12 Weiss, K. R., Chiel, H. J. and Kupfermann, I. (1986) J. Neurosci. 6, 2416-2426 13 Schwartz, J. H., Elste, A., Shapiro, E. and Gotoh, H. (1986) J. Comp. Neurol. 245, 401-421 14 Weiss, K. R., Koch, U. T., Koester, J., Rosen, S. C. and Kupfermann, I. (1982) in The Neural Basis of Feeding and Reward (Hoebel, B. G. and Novin, D., eds), pp. 25-57, Haer Institute
15 Kupfermann, I. and Weiss, K. R. (1982) Brain Res. 241, 334-337 16 Rosen, S. C., Weiss, K. R., Goldstein, R. S. and Kupfermann, I. (1989) J. Neurosci. 9, 1562-1578 17 Weiss, K. R., Shapiro, E. and Kupfermann, I. (1986) J. Neurosci. 6, 2393-2402 18 Hooper, S. L., Weiss, K. R. and Kupfermann, I. (1988) Soc. NeuroscL Abstr. 14, 608 19 Susswein, A. J. and Kupfermann, I. (1975) J. Comp. PhysioL 101,309-328 20 Chiel, H. J., Weiss, K. R. and Kupfermann, I. (1986) J. Neurosci. 6, 2427-2450 21 Katz, P. S. and Harris-Warwick, R. M. (1989) J. Neurophysiol. 62, 571-581 22 Sigvardt, K. A. and Mulloney, B. (1982) J. Exp. Biol. 97, 137-152 23 Claiborne, B. J. and Selverston, A. I. (1984) J. Neurosci. 4, 708-721 24 Chiel, H. J., Weiss, K. R. and Kupfermann, I. in Histaminergic Neurons: Morphology and Function (Watanabe, T., ed.), CRC Press (in press) 25 Pasztor, V. M. (1989) Sem. Neurosci. 1, 5-14 26 Sillar, K. T. (1989) Sem. Neurosci. 1, 45-54 27 Llin~s, R. R. (1988) Science 242, 1654-1664
Cross-modalplasticityin corticaldevelopment:differentiation and specificationof sensoryneocortex Mriganka Sur, Sarah L. Pallas and Anna W. Roe Early developmental manipulations can induce sensory afferents of one modality to project to central targets of a different sensory modal@. We and other investigators have used such cross-modal plastic@ to examine the role of afferent inputs and their patterns of activ@ in the development of sensory neocortex. We suggest that the afferent rewiring can significantly influence the internal connectivity or microcircuitry of sensory cortex, aspects of which appear to be determined or specified relatively late in development, but that they cannot influence, or influence only to a minor extent, the laminar characteristics and external connectivity patterns of cortex, which appear to be specified earlier. One of the most fundamental organizing principles of the cerebral cortex is the localization of function into different areas of representation. In recent years, a major goal of research into cortical mechanisms of sensory processing has been to define the functional role of different cortical areas within each modality. In the visual cortex of primates, for example, there are at least 17 and perhaps 30 or more areas, each of which contains a separate representation of the visual field and processes limited aspects of the visual scene 1-3. While the organization of the auditory and somatosensory cortical areas is less well understood, it is clear that at least the main features of cortical organization in these modalities are similar to those of the visual system 4. Cortical development may be thought of as a progressive restriction of the fate of cortical neurons, a process variously termed determination or specifiCorrespondence should be addressed to Mriganka Sur.
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cation. How are the sensory cortical areas specified during development, and how do they come to represent and process specific kinds of information? The most general answer is that cortical areas are specified intrinsically by genetically determined mechanisms, and/or that specification occurs by extrinsic factors that operate epigenetically. Several kinds of experiments have addressed this issue, and excellent reviews have appeareda-7; here we synthesize the results of primarily one sort of experiment that addresses the issue of cortical specification directly. These experiments involve cross-modal plasticity in development, i.e. the routing of fibers that carry information about one sensory modality into structures and central pathways that normally process a different modality. The development of a cortical area involves the specification of several features that make up the area, including the characteristics and location of its constituent cells (cytoarchitectonics), the external connections it makes with other cortical areas and subcortical structures (i.e. its inputs and outputs), and the internal connections or microcircuitry within the cortical area. Whereas other experimental paradigms can be used to address the first of these features, the induction of cross-modal plasticity provides a paradigm that is particularly suited to addressing the role of afferents in specifying the external and internal connections of a cortical area.
MngankaSur, Sarah L. Pallasand Anna W. Roeare at the Departmentof Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
S i m i l a r i t i e s and d i f f e r e n c e s b e t w e e n s e n s o r y cortical a r e a s
Any discussion of the specification of sensory cortex requires an understanding of which attributes
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The cellular and circuit properties of individual identified neurons in invertebrates can be readily studie& hence it is possible to determine how the complex properties of nerve ceils function in the generation of behavior. Recent studies of the cellular basis of feeding behavior in the marine mollusc Aplysia have focused on a neuron, C2, that has a variety of complex properties that determine the behavioral functions of the neuron. C2 conveys mechanosensory information from the mouth of the animal. It receives a complex pattern of inputs during feeding behavior, and generates diverse outputs that may shape behavior. It can act to filter out slow or sporadic sensory inputs, and its own outputs can be 'gated' by synaptic input. C2 uses histamine as its transmitter, and some of its synaptic outputs are modulatory and contribute to the expression of an arousal state induced by food. Other outputs shape feeding behavior directly by affecting motor neurons, as well as presynaptically inhibiting the outputs of feeding motor programs. Thus, the complex properties of this neuron may contribute to the flexibility and adaptability of feeding in Aplysia. Studies of C2 have expanded our concepts of the properties of sensory neurons. The complex properties of individual nerve cells contribute significantly to the information processing capacity of the nervous system. Invertebrates offer an opportunity to relate cellular properties and knowledge of connections to behavior and function. An example of this is provided by studies of an identified histaminergic neuron, C2, located in the cerebral ganglion of Aplysia. The biochemistry, pharmacology, electrophysiology, morphology and behavioral role of C2 have been studied extensively. Firing of C2 evokes a wide variety of synaptic responses in various neurons in the cerebral ganglion. These responses include fast excitation, fast inhibition, slow excitation, slow inhibition, and very slow excitation L2. Over the past 15 years, due primarily to the work of McCaman, Weinreich, Ono and their collaborators 3~9, a substantial amount of evidence has been accumulated which indicates that the various synaptic responses of C2 are mediated by the release of histamine from the neuron.
C2 receives complex excitatory and inhibitory inputs during feeding behavior When food (seaweed) stimuli are presented to the lips of the animal, C2 exhibits a burst of excitatory potentials that summate and produce action potentials in its soma. If the food is maintained on the lips, rhythmic feeding movements occur. During this behavior, C2 receives bursts of excitatory and inhibitory potentials in phase with each movement (Fig. 1) 1°. The activity of C2 is shaped by the inhibitory output of feeding motor programs The inhibitory synaptic potentials received by C2 are produced by the activity of two interneurons TINS, Vol. 13, No. 6, 1990
(B17 and B18) that are located in the buccal ganglion1]. B18 provides outputs to many cerebral cells other than C2, some of which are involved in controlling movements of the lips and tentacles of the animal11. Thus, B18, and other buccal neurons like it, may serve to 'read out' the feeding motor program onto neurons controlling muscles that must be coordinated with those of the main feeding apparatus. (See below for a discussion of the possible functional significance of these inhibitory inputs.)
C2 is a mechanoafferent and proprioceptor Every time the jaws close during the feeding program, the soma of C2 exhibits excitatory potentials 1°. These excitatory potentials have the appearance and functional properties of synaptic potentials (see below), but they are not synaptic potentials; rather, they are blocked axon spikes (A spikes). Mechanosensory information from the periphery is conveyed centrally to the soma of C2 through its peripheral axons innervating the mouth region. Action potentials in the peripheral nerves often fail to invade the soma and initial axon of C2, and are propagated passively to the soma 12.
HillelJ. Chielisat the Departmentof Biology,Case WesternReserve University,2080 AdelbertRoad, Cleveland,OH 44106, USA. KlaudiuszR. Weiss andIrving Kupfermannare at the Centerfor Neurobiologyand Behavior,New York StatePsychiatric InstituteandCollege of Physiciansand Surgeonsof Columbia University,722 West 168thStreet,New York,NY 10032, USA.
C2 can integrate, filter and gate sensory input C2 has an unusual morphology (Fig. 2). Emanating from the cell body is a very stout process that has extensive invaginations 1~,1~. The stout initial process gives off numerous fine processes that provide the synaptic output of the cell to numerous follower cells in the cerebral ganglion. More distally, the initial
MCC r
IIJJ L L Buccal mass -'-"-" pressure
--
t I
Stim
I I
II
fl
tl
i J 20 mv 5s
Fig. 1. Intracellular recordings from C2 and the metacerebral cell (MCC),
during rhythmic biting responses. The records were obtained from a 'semiintact' preparation consisting of the isolated head and the exposed cerebral ganglion. Movements of the buccal mass (the organ that grasps and swallows food) are indicated by recording the associated alterations in blood pressure as the organ moves forwards (up arrow) and backwards (down arrow). Application of a food stimulus (seaweed) results in an initial activation of C2 and the MCC, followed by rhythmic bursts of depolarizing and hyperpolarizing potentials in C2, which occur in phase with each buccal movement. The phasic activity persists for a period of time after the food is removed. (Taken, with permission, from Ref. 10.)
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process trifurcates to form very fine peripheral axons that innervate the area around the mouth. These Pattern morphological features appear to allow C2 to function generator as a gate for peripheral mechanosensory information. The gating function takes two forms. First, the cell acts as a high pass filter that permits only relatively strong and prolonged mechanostimuli to produce any synaptic outputs from the cell. Second, inhibitory synaptic input to the cell can override and 'gate out' C2 even strong stimulation. The gating properties of C2 are dependent on the fact that the cell produces synaptic output only if its peripheral axonal spikes produce full action potentials in the thick initial segment of the cell, and thereby invade the synaptic terminal region (see fight-hand traces of Fig. 2) 12. However, the initial segment of C2 is a region of low safety factor, which can cause incoming A spikes to fail (see initial potentials of the 'initial segment' trace in Fig. 2). As a consequence, the A spikes in C2 exhibit temporal and spatial summation. The cell is normally in an 'off' state and completely filters out low-intensity stimulation. The frequency and duration of firing of the peripheral axon determines whether successive A spikes will summate sufficiently to depolarize the initial segment to a level that triggers action potentials. Furthermore, A spikes from the three peripheral axons of the cell exhibit spatial summation, which also acts to overcome the blockage. The action potential in the soma and the initial process of C2 exhibit a depolarizing afterpotential; thus, once the cell is brought to threshold, subsequent A spikes ride on a depolarization, so that they more readily elicit spikes. Finally, Mouth the A spikes show a form of short-term plasticity facilitation. As the initial segment depolarizes, and the region of failure moves closer to the soma of C2, the incoming A spikes increase in size (see initial potentials of the 'initial segment' trace in Fig. 2) 12. Thus, the unique morphology of C2 causes its electrotonic inputs to manifest properties that are usually associated with chemical synaptic inputs - spatial and Fig. 2. Schematic representation of C2 and selected cells in the cerebral ganglion with which it is interconnected. The relative length of the peripheral temporal summation, and facilitation. The integrative properties of C2 also account for its axons of C2 are much longer than indicated. The figure illustrates the types of intracellular recordings that can be obtained when the mouth spontaneously sensitivity to inhibitory inputs, which may gate it on or closes or is briefly contacted with a tactile stimulus. The panels on the right off. C2 receives inhibitory synaptic input, which can illustrate hypothetical simultaneous recordings from the axon and initial significantly reduce the summation of incoming A segment of C2 (lower two panels), and from examples of two 'follower' cells of spikes, primarily by increasing the conductance of the C2 (upper two panels). The lower right panel shows that a tactile stimulus cell and enhancing the rate of decay of the A spikes. (indicated by the bar) evokes action potentials, which can be recorded in the This serves to prevent them from inducing full spikes peripheral axon of (52. The record labeled 'initial segment' illustrates that when in C2 (Ref. 12). Thus, the inhibitory synaptic input to the first spikes reach the region of the initial segment, they fail to trigger full the cell can serve to turn off the synaptic output of the spikes and appear as facilitating axon spikes (A spikes) that are electrotonically transmitted from some region in the axon (probably relatively close to the cell completely, even when the peripheral axons fire initial segment) at which spikes fail. Thus, low-frequency inputs will tend to be at moderately high rates. In fact, C2 receives two filtered out by C2. If the A spikes occur at a sufficiently high frequency, they types of inhibitory potential - a fast, discrete IPSP and summate, and in this example they reach threshold and evoke six full spikes. a more prolonged, slow IPSP 1°. The fast IPSP The upper two records illustrate that C2 can produce slow synaptic potentials inactivates C2 during a specific phase of the bite cycle, (e.g. in neuron C4 and the AACC), as well as fast synaptic potentials (e.g. in and may affect the ability of C2 to shape motor motor neuron C6), and that the synaptic output of C2 only occurs when a full outputs during feeding. In contrast, the slow IPSP spike appears in the initial segment. The diagram also shows that C2 receives may act to block the response of C2 to food-related inhibitory synaptic input from 'corollary discharge' units that are located in the stimuli completely, and thus to modulate the behavbuccal ganglion. The example given shows neuron B18. B18 can be activated in a phasic fashion by input from the pattern-generating neurons that ioral state of the animal. determine the phasing of buccal muscle contraction. The neuron also receives excitatory input from the gut. B18 inhibits C2, and excites other cerebral C2 excites an 'executor' of the feeding arousal ganglion neurons (e.g. C4). C2 probably makes presynaptic connections (filled s y s t e m C2 contributes to the arousal of feeding behavior by circles connected to C2) with the terminals of B18 and other buccal interneurons, producing presynaptic inhibition. (Based on data from Refs 11, providing slow excitatory input to the metacerebral 12 and 20.) cell (MCC), an identified serotonergic neuron that
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serves as an 'executor' of certain aspects of foodinduced arousal. The MCC acts at a variety of loci to affect feeding behavior: it can increase the activity of the central pattern generator for feeding, it provides slow excitation to feeding motor neurons, and it acts directly on muscles involved in feeding to enhance their contraction in response to excitation from motor neurons 14-16. The MCC fires when animals are exposed to food15, and its activity is enhanced by the slow, monosynaptic excitatory input from C2 (Ref. 17). The connection from C2 to the MCC has several properties appropriate for a modulatory role. The EPSP is associated with a voltage-dependent decrease of the conductance of the MCC (C2 produces a similar EPSP in C4; see Fig. 2). The EPSP becomes much larger when the MCC is depolarized. The decreased conductance also increases the effectiveness of any incoming depolarizing currents. Finally, the excitatory effect of C2 decays very slowly so that it can continue to sum over many seconds 17. Thus, even if C2 fires phasically, its primary effect on the MCC will be to increase the level of activation of the cell tonically.
C2 may act to maintain feeding arousal C2 is activated by tactile stimuli to the lips, but once the feeding motor program is active, even in the absence of food stimuli, proprioceptive inputs from the lips and jaws excite C2 during each feeding movement. Excitation of C2 increases the firing of the MCC, and the MCC activity increases the rate of the motor program output 1°. Thus, a positive feedback loop is established: feeding movements excite C2, which in turn excites the MCC, which then enhances the feeding movements that re-excite C2. Since inhibition of C2 could act to break the positive feedback loop of which it is a part, and thus decrease the food arousal of the animal, such inhibition could serve effectively to reduce arousal of the consummatory phase of feeding behavior. In fact, a neuron in the buccal ganglion, B18, monosynaptically inhibits C2 by means of a dual, fast and slow IPSP TM. As mentioned above, B18 receives phasic excitation from pattern-generating neurons during the feeding motor program. In addition, B18 is excited by stimulation of the esophageal nerve or by dilation of the gut TM. During feeding behavior in Aplysia, sensory inputs indicating that the gut has dilated may serve as a satiety signal and reduce the intensity of feeding19. C2 shapes the output of feeding musculature The synaptic actions of C2 on the MCC suggested that it was primarily responsible for slow, modulatory actions. However, its other synaptic outputs suggested that C2 might act on a more rapid time scale to shape the output of feeding motor programs. The phasic inhibition that C2 receives during each bite might then serve to sharpen the shaping function of C2, by permitting sensory information to affect follower cells only during a specific phase of the movement. Several of the neurons that receive fast, phasic synaptic input from C2 act to modulate feeding behavior. These neurons are excitatory or inhibitory motor neurons for muscles of the lips or the body wall of the head, and for muscles that connect the buccal mass to the body wall (the extrinsic muscles of the TINS, Vol. 13, No. 6, 1990
6 x Ca 2+, 3 X Mg 2+
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III [!llll[lllllllIll[[ll[[[[[lllllll[lIllll,
.....................................lllt....................................
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~
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~ .._j 5mY (C4) 20mY (B18) 5s
Fig. 3. C2 reduces the size of the EPSPin C4 evoked by firing B18. Each EPSPin C4 was evoked by triggering a single spike in B18. Note that the gain of the top record is four times that of the lower records, and that the slow sweep speed makes the EPSPsin C4 appear spike-fike. (Taken, with permission, from Ref. 11 .)
buccal mass) 2°. When C2 is fired experimentally at rates that a r e comparable to those at which it fires during feeding, it can exert effects on the feeding musculature through its synaptic followers. Extracellnlar recordings from these muscles during feeding behavior indicate that they contract in phase with the firing of C2 (Ref. 20). Thus, the phasic activation of C2 that occurs during feeding may affect the activity of feeding musculature. The muscles upon which C2 acts do not appear to be necessary for the execution of feeding responses, but instead modulate the efficiency of feeding. Removal of these muscles does not prevent animals from eating, but the amount of seaweed they ingest with each swallow is reduced 2°. Thus, these muscles appear to serve a platform or postural role, against which other muscles that mediate feeding can act to generate movements, enhancing feeding efficiency.
C2 presynaptically inhibits outputs from feeding motor p r o g r a m s While feeding motor programs shape the synaptic output of C2, the cell can reciprocally inhibit the outputs of feeding motor programs. When C2 is fired at rates observed in the semi-intact preparation, it can reduce or eliminate the phasic synaptic inputs that impinge on it and on its followers. The ability of C2 to do this is, in large part, a consequence of its actions on buccal neuron B18, whose synaptic effects on C2 and its follower cells are reduced when C2 fires (Fig. 3) 11. C2 is likely to exert at least part of its inhibitory effect directly on the presynaptic terminals of B18, because C2 reduces the synaptic output of B18 when both the cerebral and buccal ganglia are bathed in a solution that reduces or eliminates polysynaptic pathways (high divalent cation solution); also, quantal analysis (variance analysis) of the effects of C2 on the connection between B18 and cerebral neuron C4 indicates that C2 acts to reduce the number of quanta released by B18. Since histamine strongly hyperpolarizes the soma of B18, a similar action on the 225
terminals of B18 might explain the observed presynaptic action of C2 (Ref. 11). What is the physiological function of the reciprocal inhibition between C2 and buccal neuron B18? One possibility is that the reciprocal inhibition allows the animal to adapt flexibly to rapid changes in the load on its feeding apparatus that occur when it encounters unexpectedly tough pieces of food. C2 will be strongly activated by such an increased load, and may then strengthen the retraction phase of swallowing (i. e. the phase in which food is pulled into the feeding apparatus) by its actions on motor neurons, and at the same time prolong retraction by its inhibition of elements of the feeding circuitry that control protraction (i.e. the phase in which the feeding apparatus is thrust forward). Indirect evidence for this hypothesis is provided by extracellular recordings from extrinsic buccal muscle E4, whose motor neuron receives excitatory input from C2. When a piece of seaweed that an animal has swallowed is pulled, increasing the load on the feeding apparatus, muscle E4 shows large increases in its excitation, and presumably in the force that it generates 2°. Concluding remarks Studies of C2 have shed further light on the cellular basis of feeding behavior, and have more fully defined the physiological role that histamine plays in a part of the nervous system of Aplysia. The studies reviewed here indicate that C2 uses histamine as its transmitter, and that this transmitter can act rapidly or slowly to excite or inhibit a large number of other neurons in the nervous system of Aplysia. C2 is excited by mechanical stimuli and by movements of the mouth of the animal during feeding. In turn, it excites an 'executor' neuron for the feeding arousal system, the MCC. Since the MCC can further activate feeding movements, C2 may be part of a positive feedback loop that helps maintain arousal. In addition, the unusual morphology of C2 and its intrinsic properties allow it to integrate sensory information from the lips spatially and temporally, and thus serve to filter out weak inputs, while amplifying strong ones. Inhibitory input to C2 can gate it on or off. Since some of the inhibitory inputs that C2 receives are due to stretch of the gut, a signal for satiation, C2 may be part of the process that switches an animal from a state of feeding arousal to satiation. C2 can also act on the motor neurons for a variety of muscles that serve to improve the efficiency of feeding. C2 and feeding motor programs interact through reciprocal inhibition, which is likely to contribute to the adaptive flexibility that Aplysia shows during feeding. On the one hand, the motor program can act to coordinate different muscles during feeding, and suppress the activity of C2 and its followers in the appropriate phase of the behavior. On the other hand, C2 may respond to increases in the load on the feeding apparatus, and act to shape the outputs of the motor program in order to enhance an appropriate motor response to the new situation. It is interesting that recent studies on the feeding system of another invertebrate, the crab, have described cells that share a number of properties with C2 (Ref. 21). The gastropyloric receptor (GPR) cells of the crab are proprioceptors that produce both fast and slow modulatory central actions, and are involved in a 226
positive feedback loop. Another interesting parallel to the studies described here is provided by work on the inferior ventricular nerve (IVN) interneurons in another crustacean, the lobster. These neurons are mechanoreceptors that respond to stretch of the posterior part of the stomach, appear to use histamine as their transmitter, and cause shifts in the motor output of the stomatogastric ganglion through their synaptic connections within it22,23. In general, histamine appears to play complex sensory roles in a variety of different invertebrates 24. The studies of C2 and the organization of feeding behavior in Aplysia may provide more general insights into the organization of complex behavior. First, these studies strengthen the growing evidence that some sensory neurons may play a broader role than is typically assumed 25,26. Rather than faith_fully and rapidly transmitting information from the periphery, they may also preprocess it in complex ways, and act to modulate central circuitry over relatively long periods of time. Second, it is possible that, in part, arousal may be maintained in the absence of extemal sensory inputs by using proprioceptive inputs generated by the animal itself. An animal's own movements may then act to prevent the decay of arousal even when the goal object (e.g. food) becomes unavailable for a period of time. Third, the properties of C2 suggest that arousal systems may not consist of cells whose role is related solely to maintenance or regulation of arousal. Some elements of arousal systems may act both to increase arousal and to subserve a more specific modulatory effect on parts of the motor system that control a particular behavior. Finally, these data suggest one mechanism for generating flexible, adaptive behavior. Motor programs appear to use corollary discharge to coordinate a variety of different muscles during complex behaviors. However, sensors of local conditions at the different parts of the motor system that receive the motor program may suppress and override the basic program. As a consequence, specific parts of the motor system may be capable of independently adjusting their outputs as demands on that part of the system change. Studies of C2 illustrate the importance of considering the complex properties of individual nerve cells. In the past, the complexity of invertebrate nerve cells has been explained as a compensatory mechanism for generating complex behavior with relatively few nerve cells. However, studies of mammalian nerve cells have revealed that they too possess great complexity in their morphology and their conductances 27. Models of neural computation that incorporate these complexities are likely to be harder to analyse, and slower to simulate. However, their benefits may outweigh their costs: it may be easier to relate them directly to neurobiological data, and thus to test them experimentally. Most importantly, they may succeed in doing difficult computations with fewer elements.
Selected references 1 /VkCarnan, R. E. and Weinreich, D. (1985) J. Neurophysiol. 53, 1016-1037 2 0 n o , J. K. and McCaman, R. E. (1985) in Model Neural Networks and Behavior (Selverston, A. I., ecl.), pp. 303-317, Plenum Press 3 Weinreich, D., Weiner, C. and McCaman, R. (1975) Brain
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Res. 84, 341-345 4 Weinreich, D. (1977) Nature 267, 854-856 5 Weinreich, D. and Yu, Y. T. (1977) J. Neurochem. 28, 361-369 6 Weinreich, D. (1978) in Biochemistry of Characterized Neurons (Osborne, N., ed.), pp. 153-175, Pergamon 7 McCaman, R. E. and McKenna, D. G. (1978) Brain Res. 141, 165-171 8 0 n o , J. K. and McCaman, R. E. (1980) Neuroscience 5, 835-840 9 Stein, C. and Weinreich, D. (1982) J. Neurochem. 38, 204-214 10 Weiss, K. R., Chiel, H. J., Koch, U. and Kupfermann, I. (1986) J. Neurosci. 6, 2403-2415 11 Chiel, H. J., Kupfermann, I. and Weiss, K. R. (1988) J. Neurosci. 8, 49-63 12 Weiss, K. R., Chiel, H. J. and Kupfermann, I. (1986) J. Neurosci. 6, 2416-2426 13 Schwartz, J. H., Elste, A., Shapiro, E. and Gotoh, H. (1986) J. Comp. Neurol. 245, 401-421 14 Weiss, K. R., Koch, U. T., Koester, J., Rosen, S. C. and Kupfermann, I. (1982) in The Neural Basis of Feeding and Reward (Hoebel, B. G. and Novin, D., eds), pp. 25-57, Haer Institute
15 Kupfermann, I. and Weiss, K. R. (1982) Brain Res. 241, 334-337 16 Rosen, S. C., Weiss, K. R., Goldstein, R. S. and Kupfermann, I. (1989) J. Neurosci. 9, 1562-1578 17 Weiss, K. R., Shapiro, E. and Kupfermann, I. (1986) J. Neurosci. 6, 2393-2402 18 Hooper, S. L., Weiss, K. R. and Kupfermann, I. (1988) Soc. NeuroscL Abstr. 14, 608 19 Susswein, A. J. and Kupfermann, I. (1975) J. Comp. PhysioL 101,309-328 20 Chiel, H. J., Weiss, K. R. and Kupfermann, I. (1986) J. Neurosci. 6, 2427-2450 21 Katz, P. S. and Harris-Warwick, R. M. (1989) J. Neurophysiol. 62, 571-581 22 Sigvardt, K. A. and Mulloney, B. (1982) J. Exp. Biol. 97, 137-152 23 Claiborne, B. J. and Selverston, A. I. (1984) J. Neurosci. 4, 708-721 24 Chiel, H. J., Weiss, K. R. and Kupfermann, I. in Histaminergic Neurons: Morphology and Function (Watanabe, T., ed.), CRC Press (in press) 25 Pasztor, V. M. (1989) Sem. Neurosci. 1, 5-14 26 Sillar, K. T. (1989) Sem. Neurosci. 1, 45-54 27 Llin~s, R. R. (1988) Science 242, 1654-1664
Cross-modalplasticityin corticaldevelopment:differentiation and specificationof sensoryneocortex Mriganka Sur, Sarah L. Pallas and Anna W. Roe Early developmental manipulations can induce sensory afferents of one modality to project to central targets of a different sensory modal@. We and other investigators have used such cross-modal plastic@ to examine the role of afferent inputs and their patterns of activ@ in the development of sensory neocortex. We suggest that the afferent rewiring can significantly influence the internal connectivity or microcircuitry of sensory cortex, aspects of which appear to be determined or specified relatively late in development, but that they cannot influence, or influence only to a minor extent, the laminar characteristics and external connectivity patterns of cortex, which appear to be specified earlier. One of the most fundamental organizing principles of the cerebral cortex is the localization of function into different areas of representation. In recent years, a major goal of research into cortical mechanisms of sensory processing has been to define the functional role of different cortical areas within each modality. In the visual cortex of primates, for example, there are at least 17 and perhaps 30 or more areas, each of which contains a separate representation of the visual field and processes limited aspects of the visual scene 1-3. While the organization of the auditory and somatosensory cortical areas is less well understood, it is clear that at least the main features of cortical organization in these modalities are similar to those of the visual system 4. Cortical development may be thought of as a progressive restriction of the fate of cortical neurons, a process variously termed determination or specifiCorrespondence should be addressed to Mriganka Sur.
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cation. How are the sensory cortical areas specified during development, and how do they come to represent and process specific kinds of information? The most general answer is that cortical areas are specified intrinsically by genetically determined mechanisms, and/or that specification occurs by extrinsic factors that operate epigenetically. Several kinds of experiments have addressed this issue, and excellent reviews have appeareda-7; here we synthesize the results of primarily one sort of experiment that addresses the issue of cortical specification directly. These experiments involve cross-modal plasticity in development, i.e. the routing of fibers that carry information about one sensory modality into structures and central pathways that normally process a different modality. The development of a cortical area involves the specification of several features that make up the area, including the characteristics and location of its constituent cells (cytoarchitectonics), the external connections it makes with other cortical areas and subcortical structures (i.e. its inputs and outputs), and the internal connections or microcircuitry within the cortical area. Whereas other experimental paradigms can be used to address the first of these features, the induction of cross-modal plasticity provides a paradigm that is particularly suited to addressing the role of afferents in specifying the external and internal connections of a cortical area.
MngankaSur, Sarah L. Pallasand Anna W. Roeare at the Departmentof Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
S i m i l a r i t i e s and d i f f e r e n c e s b e t w e e n s e n s o r y cortical a r e a s
Any discussion of the specification of sensory cortex requires an understanding of which attributes
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