THE JOURNAL OF COMPARATIVE NEUROLOGY 323:167-197 (1992)
The Organization of the Thalamocortical Connections of the Mediodorsal Thalamic Nucleus in the Rat, Related to the Ventral Forebrain-Prefrontal Cortex Topography JAMES P. RAY
AND
JOSEPH L. PRICE
Department of Anatomy & Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110
ABSTRACT The medial and central segments of the mediodorsal nucleus of the thalamus (MD) receive afferents from the ventral forebrain, including the piriform cortex, the ventral pallidum, and the amygdaloid complex. Because MD is reciprocally interconnected with prefrontal and agranular insular cortical areas, it provides a relay of ventral forebrain activity to these cortical areas. However, there are also direct projections from the piriform cortex and the amygdala to the prefrontal and agranular insular cortices. This study addresses whether this system has a “triangular” organization, such that structures in the ventral forebrain project to interconnected areas in MD and the prefrontali insular cortex. The thalamocortical projections of MD have been studied in experiments with injections of retrograde tracers into prefrontal or agranular insular cortical areas. In many of the same experiments, projections from the ventral forebrain to MD and to the prefrontali insular cortex have been demonstrated with anterograde axonal tracers. The connections of the piriform cortex (PC) with MD and the prefrontaliinsular cortex form an organized triangular system. The PC projections to the central and medial segments of MD and to the lateral orbital cortex (LO) and the ventral and posterior agranular insular cortices (AI, and Alp) are topographically organized, such that more caudal parts of PC tend to project more medially in MD and more caudally within the orbital/insular cortex. The central and medial portions of MD also send matching, topographically organized projections to LO, AI, and AI,, with more medial parts of MD projecting further caudally. The anterior cortical nucleus of the amygdala (CO,) also projects to the dorsal part of the medial segment of MD and to its cortical targets, the medial orbital area (MO) and AT,. The projections of the basaliaccessory basal amygdaloid nuclei to MD and to prefrontal cortex, and from MD to amygdaloceptiveparts of prefrontal cortex, are not as tightly organized. Amygdalothalamic afferents in MD are concentrated in the dorsal half of the medial segment. Cells in this part of the nucleus project to the amygdaloceptive prelimbic area (PL) and AI,. However, other amygdaloceptive prefrontal areas are connected to parts of MD that do not receive fibers from the amygdala. Ventral pallidal afferents are distributed to all parts of the central and medial segments of MD, overlapping with the fibers from the amygdala and piriform cortex. Fibers from other parts of the pallidum, or related areas such as the substantia nigra, pars reticulata, terminate in the lateral and ventral parts of MD, where they overlap with inputs from the superior colliculus and other brainstem structures. Thus, pallidal or pallidum-related inputs overlap with other 19% Wiley-Liss, Inc afferents in all parts of MD. 1
Key words: amygdala, piriform cortex, ventral pallidum, agranular insular cortex
Accepted May 15,1992 Address reprint requests to Dr. Joseph L. Price, Department of Anatomy & Neurobiology, Washington University School of Medicine, 660 S.Euclid Avenue, St. Louis, MO 63110.
c 1992 WILEY-LISS, INC.
J.P. RAY AND J.1,. PRICE
168
"Ventral forebrain" is a topographic term referring to ventral, non-neocortical portions of the telencephalon. It includes at least four distinct, yet anatomically interconnected, systems: the olfactory bulb and its projection field, the primary olfactory cortex, including the piriform and entorhinal cortices; the amygdaloid complex and "extended amygdala" (Alheid and Heimer, '88); the ventral striatal and pallidal structures, such as the nucleus accumbens, and the superficial and deeper layers of the olfactory tubercle; and the nucleus basalis and the diagonal band nuclei. Each of these four diverse systems sends a projection to the medial or central segments of the mediodorsal nucleus of the thalamus (Nauta, '61; Powell et al., '65; Krettek and Price, '77b; Benjamin et al., '82; Price and Slotnick, '83; Aggleton and Mishkin, '84; Velayos and Reinoso-Suarez, '85; Ono and Niimi, '86; Mogenson et al., '87; Russchen et al., '87; Groenewegen, '88; Hreib et al., '88; Ray et al., '92). The mediodorsal nucleus (MD), in turn, is reciprocally interconnected with the prefrontal and agranular insular cortices (Leonard, '69; Krettek and Price, '77a; Divac et al., '78; Markowitsch et al., '78; Goldman-Rakic and Porrino, '85; Velayos and Reinoso-Suarez, '85; Russchen et al., '87; Groenewegen, '88); its dense thalamocortical projection thus hypothetically represents a means by which the ventral forebrain can influence prefrontal cortical and agranular insular function.
However, another aspect of the organization of the ventral forebrain-MD-prefrontal cortical system has been less fully appreciated; namely, many of the areas that project to MD, such as the amygdala and the piriform cortex, also project directly to the prefrontal cortex. These cortical projections are robust, and more dense than the corresponding projection to the mediodorsal nucleus. They also show specificity, terminating with a characteristic laminar pattern in specific areas of the prefrontal cortex. Projections of the basal amygdaloid nucleus to the prefrontal cortex in the rat terminate in the prelimbic and infr-
The Organization of the Thalamocortical Connections of the Mediodorsal Thalamic Nucleus in the Rat, Related to the Ventral Forebrain-Prefrontal Cortex Topography JAMES P. RAY
AND
JOSEPH L. PRICE
Department of Anatomy & Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110
ABSTRACT The medial and central segments of the mediodorsal nucleus of the thalamus (MD) receive afferents from the ventral forebrain, including the piriform cortex, the ventral pallidum, and the amygdaloid complex. Because MD is reciprocally interconnected with prefrontal and agranular insular cortical areas, it provides a relay of ventral forebrain activity to these cortical areas. However, there are also direct projections from the piriform cortex and the amygdala to the prefrontal and agranular insular cortices. This study addresses whether this system has a “triangular” organization, such that structures in the ventral forebrain project to interconnected areas in MD and the prefrontali insular cortex. The thalamocortical projections of MD have been studied in experiments with injections of retrograde tracers into prefrontal or agranular insular cortical areas. In many of the same experiments, projections from the ventral forebrain to MD and to the prefrontali insular cortex have been demonstrated with anterograde axonal tracers. The connections of the piriform cortex (PC) with MD and the prefrontaliinsular cortex form an organized triangular system. The PC projections to the central and medial segments of MD and to the lateral orbital cortex (LO) and the ventral and posterior agranular insular cortices (AI, and Alp) are topographically organized, such that more caudal parts of PC tend to project more medially in MD and more caudally within the orbital/insular cortex. The central and medial portions of MD also send matching, topographically organized projections to LO, AI, and AI,, with more medial parts of MD projecting further caudally. The anterior cortical nucleus of the amygdala (CO,) also projects to the dorsal part of the medial segment of MD and to its cortical targets, the medial orbital area (MO) and AT,. The projections of the basaliaccessory basal amygdaloid nuclei to MD and to prefrontal cortex, and from MD to amygdaloceptiveparts of prefrontal cortex, are not as tightly organized. Amygdalothalamic afferents in MD are concentrated in the dorsal half of the medial segment. Cells in this part of the nucleus project to the amygdaloceptive prelimbic area (PL) and AI,. However, other amygdaloceptive prefrontal areas are connected to parts of MD that do not receive fibers from the amygdala. Ventral pallidal afferents are distributed to all parts of the central and medial segments of MD, overlapping with the fibers from the amygdala and piriform cortex. Fibers from other parts of the pallidum, or related areas such as the substantia nigra, pars reticulata, terminate in the lateral and ventral parts of MD, where they overlap with inputs from the superior colliculus and other brainstem structures. Thus, pallidal or pallidum-related inputs overlap with other 19% Wiley-Liss, Inc afferents in all parts of MD. 1
Key words: amygdala, piriform cortex, ventral pallidum, agranular insular cortex
Accepted May 15,1992 Address reprint requests to Dr. Joseph L. Price, Department of Anatomy & Neurobiology, Washington University School of Medicine, 660 S.Euclid Avenue, St. Louis, MO 63110.
c 1992 WILEY-LISS, INC.
J.P. RAY AND J.1,. PRICE
168
"Ventral forebrain" is a topographic term referring to ventral, non-neocortical portions of the telencephalon. It includes at least four distinct, yet anatomically interconnected, systems: the olfactory bulb and its projection field, the primary olfactory cortex, including the piriform and entorhinal cortices; the amygdaloid complex and "extended amygdala" (Alheid and Heimer, '88); the ventral striatal and pallidal structures, such as the nucleus accumbens, and the superficial and deeper layers of the olfactory tubercle; and the nucleus basalis and the diagonal band nuclei. Each of these four diverse systems sends a projection to the medial or central segments of the mediodorsal nucleus of the thalamus (Nauta, '61; Powell et al., '65; Krettek and Price, '77b; Benjamin et al., '82; Price and Slotnick, '83; Aggleton and Mishkin, '84; Velayos and Reinoso-Suarez, '85; Ono and Niimi, '86; Mogenson et al., '87; Russchen et al., '87; Groenewegen, '88; Hreib et al., '88; Ray et al., '92). The mediodorsal nucleus (MD), in turn, is reciprocally interconnected with the prefrontal and agranular insular cortices (Leonard, '69; Krettek and Price, '77a; Divac et al., '78; Markowitsch et al., '78; Goldman-Rakic and Porrino, '85; Velayos and Reinoso-Suarez, '85; Russchen et al., '87; Groenewegen, '88); its dense thalamocortical projection thus hypothetically represents a means by which the ventral forebrain can influence prefrontal cortical and agranular insular function.
However, another aspect of the organization of the ventral forebrain-MD-prefrontal cortical system has been less fully appreciated; namely, many of the areas that project to MD, such as the amygdala and the piriform cortex, also project directly to the prefrontal cortex. These cortical projections are robust, and more dense than the corresponding projection to the mediodorsal nucleus. They also show specificity, terminating with a characteristic laminar pattern in specific areas of the prefrontal cortex. Projections of the basal amygdaloid nucleus to the prefrontal cortex in the rat terminate in the prelimbic and infr-
