RESEARCH HIGHLIGHTS Nature Reviews Neuroscience | AOP, published online 30 October 2013; doi:10.1038/nrn3629
SYNAPTIC TRANSMISSION
Releasing the brakes Further analysis revealed a temporal sequence of excitation followed by inhibition and then excitation — a classic signature of disinhibition
Not much is known about which interneuron subtypes operate in specific cortical microcircuits. Two recent studies, however, reveal that vasoactive intestinal polypeptide (VIP)-expressing interneurons enhance cortical activity and influence behaviour by disinhibiting excitatory cortical neurons. In the cortex, VIP interneurons synapse mostly onto somatostatin (SOM)-expressing and a portion of parvalbumin (PV)-expressing interneurons that inhibit pyramidal cells. Pi et al. selectively expressed the light-activated cation channel channelrhodopsin 2 in VIP interneurons. Brief light stimulation of these neurons decreased firing in other interneurons but increased firing in pyramidal cells in both the auditory cortex (AC) and the medial prefrontal cortex (mPFC). Further analysis revealed a temporal sequence of excitation followed by inhibition and then excitation — a classic signature of disinhibition. Furthermore, photoactivation of VIP neurons in brain slices evoked inhibitory postsynaptic currents in SOM and PV neurons in the AC and mPFC and enhanced FOS expression (a marker of neuronal activity) in pyramidal cells in the mPFC.
Next, the authors turned their attention to the behavioural conditions under which VIP neurons are recruited. First, Pi et al. established that disinhibition by VIP neurons enhanced the functionally specific subpopulation of pyramidal cells that are responsive to tones in the AC. To determine the behavioural significance of this effect, the authors used a go–no-go auditory discrimination task and found that positive or negative reinforcement signals, such as reward and punishment, resulted in strong activation of VIP interneurons. In a separate study, Lee et al. found a disinhibitory circuit involving VIP interneurons in the somatosensory cortex. These authors were interested in how projections from the primary vibrissal motor cortex (vM1) modulate activity in the primary somatosensory barrel cortex (S1). Reciprocal connections between these two areas are important for sensorimotor integration, which is important for sensory perception and the proper execution of motor tasks. However, neither the precise connectivity nor the mechanisms of sensory processing in this pathway are well understood. It had previously been demonstrated that whisking behaviour
correlates with the activity of certain types of interneurons in S1. Lee et al. used an optogenetic approach to selectively activate S1-projecting vM1 pyramidal neurons and recorded activity in different neuronal subtypes in S1. They found that activity in the vM1–S1 pathway recruited VIP interneurons in S1 more strongly than either pyramidal cells or other interneuron types, and that these VIP neurons inhibit SOM interneurons more strongly than other interneuron types or pyramidal cells. Spontaneous whisking results in increased activity of excitatory neurons in vM1, and the authors reasoned that this was likely to result in increased activity in S1. In vivo recordings from VIP and SOM interneurons showed that whisking behaviour was correlated with increased spiking in VIP neurons and inversely correlated with SOM interneuron activity. Inhibiting vM1 activity caused a reduction in the correlation between whisking and increased activity of VIP neurons and between whisking and decreased activity of SOM interneurons, suggesting that these effects rely on direct excitatory inputs from vM1. Overall, these data suggest that the increased activity in vM1 caused by whisking recruits VIP inter neurons, which in turn inhibit SOM interneurons. These studies reveal novel roles for VIP interneurons in cortical microcircuits. The existence of similar circuits in three distinct cortical areas suggests that VIP interneurons could be part of a conserved mechanism for disinhibitory regulation of neuronal processing in the neocortex. Sian Lewis ORIGINAL RESEARCH PAPERS Pi, H.-J. et al. Cortical interneurons that specialize in disinhibitory control. Nature http://dx.doi. org/10.1038/nature12676 (2013) | Lee, S. et al. A disinhibitory circuit mediates motor integration in the somatosensory cortex. Nature Neurosci. http://dx.doi.org/10.1038/nn.3544 (2013)
DIGITAL VISION
NATURE REVIEWS | NEUROSCIENCE
VOLUME 14 | DECEMBER 2014 © 2013 Macmillan Publishers Limited. All rights reserved
SYNAPTIC TRANSMISSION
Releasing the brakes Further analysis revealed a temporal sequence of excitation followed by inhibition and then excitation — a classic signature of disinhibition
Not much is known about which interneuron subtypes operate in specific cortical microcircuits. Two recent studies, however, reveal that vasoactive intestinal polypeptide (VIP)-expressing interneurons enhance cortical activity and influence behaviour by disinhibiting excitatory cortical neurons. In the cortex, VIP interneurons synapse mostly onto somatostatin (SOM)-expressing and a portion of parvalbumin (PV)-expressing interneurons that inhibit pyramidal cells. Pi et al. selectively expressed the light-activated cation channel channelrhodopsin 2 in VIP interneurons. Brief light stimulation of these neurons decreased firing in other interneurons but increased firing in pyramidal cells in both the auditory cortex (AC) and the medial prefrontal cortex (mPFC). Further analysis revealed a temporal sequence of excitation followed by inhibition and then excitation — a classic signature of disinhibition. Furthermore, photoactivation of VIP neurons in brain slices evoked inhibitory postsynaptic currents in SOM and PV neurons in the AC and mPFC and enhanced FOS expression (a marker of neuronal activity) in pyramidal cells in the mPFC.
Next, the authors turned their attention to the behavioural conditions under which VIP neurons are recruited. First, Pi et al. established that disinhibition by VIP neurons enhanced the functionally specific subpopulation of pyramidal cells that are responsive to tones in the AC. To determine the behavioural significance of this effect, the authors used a go–no-go auditory discrimination task and found that positive or negative reinforcement signals, such as reward and punishment, resulted in strong activation of VIP interneurons. In a separate study, Lee et al. found a disinhibitory circuit involving VIP interneurons in the somatosensory cortex. These authors were interested in how projections from the primary vibrissal motor cortex (vM1) modulate activity in the primary somatosensory barrel cortex (S1). Reciprocal connections between these two areas are important for sensorimotor integration, which is important for sensory perception and the proper execution of motor tasks. However, neither the precise connectivity nor the mechanisms of sensory processing in this pathway are well understood. It had previously been demonstrated that whisking behaviour
correlates with the activity of certain types of interneurons in S1. Lee et al. used an optogenetic approach to selectively activate S1-projecting vM1 pyramidal neurons and recorded activity in different neuronal subtypes in S1. They found that activity in the vM1–S1 pathway recruited VIP interneurons in S1 more strongly than either pyramidal cells or other interneuron types, and that these VIP neurons inhibit SOM interneurons more strongly than other interneuron types or pyramidal cells. Spontaneous whisking results in increased activity of excitatory neurons in vM1, and the authors reasoned that this was likely to result in increased activity in S1. In vivo recordings from VIP and SOM interneurons showed that whisking behaviour was correlated with increased spiking in VIP neurons and inversely correlated with SOM interneuron activity. Inhibiting vM1 activity caused a reduction in the correlation between whisking and increased activity of VIP neurons and between whisking and decreased activity of SOM interneurons, suggesting that these effects rely on direct excitatory inputs from vM1. Overall, these data suggest that the increased activity in vM1 caused by whisking recruits VIP inter neurons, which in turn inhibit SOM interneurons. These studies reveal novel roles for VIP interneurons in cortical microcircuits. The existence of similar circuits in three distinct cortical areas suggests that VIP interneurons could be part of a conserved mechanism for disinhibitory regulation of neuronal processing in the neocortex. Sian Lewis ORIGINAL RESEARCH PAPERS Pi, H.-J. et al. Cortical interneurons that specialize in disinhibitory control. Nature http://dx.doi. org/10.1038/nature12676 (2013) | Lee, S. et al. A disinhibitory circuit mediates motor integration in the somatosensory cortex. Nature Neurosci. http://dx.doi.org/10.1038/nn.3544 (2013)
DIGITAL VISION
NATURE REVIEWS | NEUROSCIENCE
VOLUME 14 | DECEMBER 2014 © 2013 Macmillan Publishers Limited. All rights reserved
