Role of the limbic system in hypothalamically elicited attack behavior

The present review summarizes our research findings concerning the role of the limbic system in hypothalamically-elicited aggression in the cat. Utilizing a dual-stimulation procedure, our results indicate that much of the limbic system suppresses quiet biting attack behavior. The most potent inhibitory effects were obtained from the basomedial amygdala and the prefrontal cortex. Other structures displaying suppression of attack following electrical stimulation include the dorsal hippocampus, pyriform cortex, lateral septal nucleus, lateral aspect of substantia innominata, and anterior cingulate gyrus. Sites producing facilitation of attack include the ventral hippocampus, far lateral aspect of the lateral septal nucleus, medial aspect of the substantia innominata, and lateral amygdaloid nucleus. Anatomical studies suggest that the medial forebrain bundle and stria terminalis are utilized by limbic structures to provide direct modulation of the hypothalamus while the substantia innominata, mediodorsal thalamic nucleus and bed nucleus of the stria terminalis contain important interneurons in the control of quiet biting attack. Further studies indicate that the amygdala, ventral hippocampus, and substantia innominata may control aggressive behavior by modulating the trigeminal sensory components of the attack response.     

Hodological characterization of the septum in anuran amphibians: II. Efferent connections

The efferent connections of the septum of the gray treefrog Hyla versicolor were studied by combining anterograde and retrograde tracing with biotin ethylendiamine (Neurobiotin). The lateral septal complex projects mainly to the medial pallium, limbic regions (e.g., amygdala and nucleus accumbens), and hypothalamic areas but also to sensory nuclei in the diencephalon and midbrain. The central septal complex strongly innervates the medial pallium, limbic, and hypothalamic areas but also specific sensory (including olfactory) regions. The medial septal complex sends major projections to all olfactory nuclei and a weaker projection to the hypothalamus. Our results indicate that all septal nuclei may modify the animal's internal state via efferents to limbic and hypothalamic areas. Via projections to the medial pallium, lateral and central septal complexes may be involved in learning processes as well. Because of their connections to specific sensory areas, all septal areas are in a position to influence sensory processing. Furthermore, our data suggest that both the postolfactory eminence and the bed nucleus of the pallial commissure are not part of the septal complex, rather, the postolfactory eminence seems to be comparable to the mammalian primary olfactory cortex, whereas the bed nucleus may be analogous to the mammalian subfornical organ.     

Oxytocin and vasopressin immunoreactivity within the forebrain and limbic-related areas in the mustached bat, Pteronotus parnellii

The nonapeptides, oxytocin and arginine vasopressin, play an important role in mammalian social and reproductive behavior. Using immunocytochemical procedures, we identified oxytocin-immunoreactive neurons in the frontal and auditory cortices, limbic areas such as the medial septal nucleus, horizontal limb of the diagonal band and the amygdala. Only arginine vasopressin neurons were present in the bed nucleus of the stria terminalis. In limbic-related areas, the hypothalamic paraventricular and supraoptic nuclei and the nucleus centralis contained both oxytocin and arginine vasopressin neurons. The medial preoptic area showed a positive reaction for several arginine vasopressin fibers, but not oxytocin fibers, except in one female bat sacrificed during the breeding season. Arginine vasopressin fibers were observed in another limbic-related area, the periaqueductal gray. Furthermore, oxytocin was predominantly localized within sensory (e.g., auditory) and frontal cortex and limbic areas, whereas arginine vasopressin was restricted largely to known audiovocal regions of the periaqueductal gray. Classical neurosecretory nuclei in the hypothalamus contain both peptides. Oxytocin-immunoreactive neurons were also found in other structures such as the olfactory bulb, olfactory tubercle, primary and secondary motor cortex, fronto-parietal cortex, piriform cortex and the nucleus of the internal capsule. Both oxytocin and arginine vasopressin immunoreactivity was present in the suprachiasmatic nucleus, median eminence, neural lobe of the hypophysis and the pineal gland. Together with previous studies, the presence of these peptides within auditory areas of the cortex (sensory and frontal), and limbic as well as limbic-related regions provides anatomical evidence supporting their proposed role in social vocal behaviors and probably in auditory processing.     

A [14C]2-deoxyglucose analysis of the functional neural pathways of the limbic forebrain in the rat. V. The septal area

The [14C]2-deoxyglucose (2-DG) metabolic mapping technique has been used to identify the regions responding with an augmented rate of metabolism following focal electrical stimulation of various sites within the lateral septal nucleus and medial septal nucleus/diagonal band (MSN/DB) complex in the rat. Since 2-DG uptake has been correlated with rates of functional activity, it was the intention of this study to suggest the anatomical substrates underlying various physiological and behavioral responses elicited by stimulation of the septal area. The results show that stimulation of any region within the lateral septal nucleus produced a profound bilateral activation of both the lateral septal nucleus, as well as the hippocampal formation. While stimulation of a number of different fiber systems associated with the lateral septum could contribute to the observed pattern of labeling, the data suggest that, functionally, a major consequence of such stimulation is the antidromic activation of CA3----lateral septum fibers to axonal branch points, beyond which, orthodromic propagation of the impulse produces activation in CA3 target regions, including subfields CA1 and CA3, as well as the lateral septal nucleus, bilaterally. In addition, regions typically manifesting metabolic activation following stimulation of the lateral septal nucleus included the ipsilateral diagonal band of Broca, nucleus accumbens, lateral preoptic area and lateral hypothalamus, posteriorly, and the prelimbic cortex, anteriorly. Occasionally, target regions of the postcommissural fornix, including the medial mammillary nucleus and anterior thalamic nuclei were also activated following stimulation of the lateral septal nucleus. In contrast to the widespread pattern of activation resulting from stimulation of the lateral septal nucleus, stimulation of the MSN/DB complex produced activation which was largely confined to the medial forebrain bundle. In a final phase of the experiment, afterdischarge activity was elicited by sodium penicillin injection into the lateral septal nucleus. Such treatment produced more widespread 2-DG uptake, including more extensive activation within the lateral septal nucleus, hippocampal formation, amygdala, and thalamus. Additionally, the prefrontal cortex and temporal neocortex were activated.     

Neuroanatomical structures involved in the action of the 5-HT3 antagonist ondansetron: a 2-deoxyglucose autoradiographic study in the rat

Local cerebral glucose utilization following the acute administration of the 5-HT3 receptor antagonist ondansetron (0.01-1.0 mg/kg) was determined using [14C]2-deoxyglucose quantitative autoradiography. Ondansetron effected alterations in 13 of the 66 brain areas analyzed including limbic, auditory and visual structures. In the majority of these 13 regions ondansetron was only effective at reducing glucose use compared to control values at a dose of 0.01 mg/kg. Thus in limbic and related areas (CA2 and CA3 fields of the hippocampus, lateral habenula and septal nucleus) glucose utilization was reduced by 15-21%. Similar reductions (18-20%) were apparent in primary auditory and visual areas (auditory cortex, medial geniculate and visual cortex). However, with the exception of the ventromedial thalamic nucleus (14% reduction) glucose use in extrapyramidal and sensory motor areas was unchanged. Following larger doses of ondansetron (0.1 and 1.0 mg/kg), there was no change in cerebral glucose utilization relative to control values, with the exception of the median raphe. In this structure local cerebral glucose utilization was significantly increased (P less than 0.05) following administration of 1.0 mg/kg ondansetron relative to the lower dose of 0.01 mg/kg. Changes in glucose use did not always reflect areas of high 5-HT3 receptor density. Thus, although cerebral glucose use was reduced in hippocampal layers, it was unchanged in the entorhinal cortex and the area postrema. These data suggest that under these experimental conditions ondansetron produces modest changes in glucose utilization which are primarily confined to limbic structures and those involved in sensory processing.     

A[C]2-deoxyglucose analysis of the functional neural pathways of the limbic forebrain in the rat. V. the septal area

The [¹⁴C]2-deoxyglucose (2-DG) metabolic mapping technique has been used to identify the regions responding with an augmented rate of metabolism following focal electrical stimulation of various sites within the lateral septal nucleus and medial septal nucleus/diagonal band (MSN/DB) complex in the rat. Since 2-DG uptake has been correlated with rates of functional activity, it was the intention of this study to suggest the anatomical substrates underlying various physiological and behavioral responses elicited by stimulation of the septal area. The results show that stimulation of any region within the lateral septal nucleus produced a profound bilateral activation of both the lateral septal nucleus, as well as the hippocampal formation. While stimulation of a number of different fiber systems associated with the lateral septum could contribute to the observed pattern of labeling, the data suggest that, functionally, a major consequence of such stimulation is the antidromic activation of CA3 → lateral septum fibers to axonal branch points, beyond which, orthodromic propagation of the impulse produces activation in CA3 target regions, including subfields CA1 and CA3, as well as the lateral septal nucleus, bilaterally. In addition, regions typically manifesting metabolic activation following stimulation of the lateral septal nucleus included the ipsilateral diagonal band of Broca, nucleus accumbens, lateral preoptic area and lateral hypothalamus, posteriorly, and the prelimbic cortex, anteriorly. Occasionally, target regions of the postcommissural fornix, including the medial mammillary nucleus and anterior thalamic nuclei were also activated following stimulation of the lateral septal nucleus. In contrast to the widespread pattern of activation resulting from stimulation of the lateral septal nucleus stimulation of the MSN/DB complex produced activation which was largely confined to the mediall forebrain bundle. In a final phase of the experiment, afterdischarge activity was elicited by sodium penicillin injection into the lateral septal nucleus. Such treatment produced more widespread 2-DG uptake, including more extensive activation within the lateral septal nucleus, hippocampal formation, amygdala, and thalamus. Additionally, the prefrontal cortex and temporal neocortex were activated.     

The connections of the septal region in the rat

The efferent, afferent and intrinsic connections of the septal region have been analyzed in the rat with the autoradiographic method. The lateral septal nucleus, which can be divided into dorsal, intermediate and ventral parts, receives its major input from the hippocampal formation and projects to the medial septal-diagonal band complex. The ventral part of the nucleus also sends fibers through the medial forebrain bundle to the medial preoptic and anterior hypothalamic areas, to the lateral hypothalamic area and the dorsomedial nucleus, to the mammillary body (including the supramammillary region), and to the ventral tegmental area. The medial septal nucleus/diagonal band complex projects back to the hippocampal formation by way of the dorsal fornix, fimbria, and possibly the cingulum. Both nuclei also project through the medial forebrain bundle to the medial and lateral preoptic areas, to the lateral hypothalamic area, and to the mammillary complex. The medial septal nucleus also sends fibers to the midbrain (the ventral tegmental area and raphe nuclei) and to the parataenial nucleus of the thalamus, while the nucleus of the diagonal band has an additional projection to the anterior limbic area. Ascending inputs to the medial septal nucleus/diagonal band complex arise in several hypothalamic nuclei and in the brainstem aminergic cell groups. The posterior septal nuclei (the septofimbrial and triangular nuclei) receive their major input from the hippocampal formation, and project in a topographically ordered manner upon the habenular nuclei and the interpeduncular nuclear complex. The bed nucleus of the stria terminalis receives its major input from the amygdala (Krettek and Price, '78); but other afferents arise from the ventral subiculum, the ventromedial nucleus, and the brainstem aminergic cell groups. The principal output of the bed nucleus is through the medial forebrain bundle to the substantia innominata, the nucleus accumbens, most parts of the hypothalamus and the preoptic area, the central tegmental fields of the midbrain, the ventral tegmental area, the dorsal and median nuclei of the raphe, and the locus coeruleus. The bed nucleus also projects to the anterior nuclei of the thalamus, the parataenial and paraventricular nuclei, and the medial habenular nucleus, and through the stria terminalis to the medial and central nuclei of the amygdala, and to the amygdalo-hippocampal transition area.     

Antinociception and behavioral changes induced by carbachol microinjected into identified sites of the rat brain

The sites of the rat brain in which intracerebral administration of carbachol (0.4 microgram/0.5 microliter) elevates the nociceptive threshold to thermic (tail-flick test) and mechanical (calibrated-pinch test) noxious stimuli were examined. An extensive mapping (510 sites) ranging from AP + 10.5 to AP-0.1 mm revealed that antinociception was obtained from 119 sites (23%) widely scattered in the brain, and reached structures distant from, or within the immediate vicinity of the ventricular system. The effects from most placement were demonstrated using the tail-flick test, whereas a smaller proportion (approximately 13%) of sites was effective in reducing the response to mechanical stimuli only. Structures containing sensitive sites include the dorsal raphe nucleus, lateral border of the superior cerebellar peduncle, caudal portion of the superior colliculus, medial geniculate body, habenular complex, amygdala, temporal pole of the ventral hippocampus, rostral aspect of the dorsal hippocampus, lateral septal area, and triangular nucleus of the septum. Analysis of the distribution of responsive sites indicated that they are poorly superposed to the known distribution of opiate-sensitive areas. Most of the structures found to be responsive to carbachol are also known to possess cholinergic receptors and to evoke antinociception following focal electrical stimulation. In various placements, particularly in limbic structures, microinjection of carbachol evoked jumping to mechanical noxious stimulation, hyperexcitability to non-noxious stimuli, convulsive reactions, and other less frequent reactions. On few occasions, however, these changes were accompanied by antinociception.     

Afferent connections of the sexually dimorphic area of the hypothalamus of male and female gerbils

We studied neural inputs to the sexually dimorphic area (SDA) of the gerbil hypothalamus by injecting wheat-germ agglutinin-horseradish peroxidase into its medial or lateral components in males and females. To confirm the topography of SDA afferents, we injected Phaseolus vulgaris-leucoagglutinin into areas where retrograde labeling from the medial and lateral SDA differed. Both methods indicated that the medial SDA received stronger inputs from the medial part of the bed nucleus of the stria terminalis, the ventral part of the lateral septal nucleus, the medial amygdaloid nucleus, and the amygdalohippocampal area, than the lateral SDA does. In contrast, the rostrodorsal part of the lateral septum, the lateral part of the bed nucleus of the stria terminalis, the anterior and posterior hypothalamic areas, and the dorsomedial hypothalamic nucleus project more heavily to the lateral than to the medial SDA. In addition, retrograde labeling suggested that the ventral part of the premammillary nucleus projects more strongly to the medial than to the lateral SDA, whereas the infralimbic area of the cortex and the lateral preoptic area project more strongly to the lateral than to the medial SDA. The densities of cells in the bed nucleus of the stria terminalis and medial amygdaloid nucleus that could be retrogradely labeled from the medial SDA were greater in males than in females. This was not true of labeling in the arcuate nucleus or in the ventral part of the lateral septal nucleus. Since the medial SDA receives strong inputs from areas with many steroid-accumulating cells, it could respond to steroids directly and via these afferents. In contrast, hormonal effects on the lateral SDA are more likely to occur locally.     

Hodological characterization of the septum in anuran amphibians: I. Afferent connections

On the basis of Nissl-stained sections, we subdivided the septum of the gray treefrog Hyla versicolor in the lateral, central, and medial septal complex. The afferent projections of the different septal nuclei were studied by combined retrograde and anterograde tracing with biotin ethylendiamine (Neurobiotin). The central and medial septal complex receives direct input from regions of the olfactory bulb and from all other limbic structures of the telencephalon (e.g., amygdalar regions, nucleus accumbens), whereas projections to the lateral septal complex are absent or less extensive. The medial pallium projects to all septal nuclei. In the diencephalon, the anterior thalamic nucleus provides the main ascending input to all subnuclei of the anuran septum, which can be interpreted as a limbic/associative pathway. The ventromedial thalamic nucleus projects to the medial and lateral septal complex and may thereby transmit multisensory information to the limbic system. Anterior preoptic nucleus, suprachiasmatic nucleus, and hypothalamic nuclei innervate the central and lateral septal complex. Only the nuclei of the central septal complex receive input from the brainstem. Noteworthy is the relatively strong projection from the nucleus raphe to the central septal complex, but not to the other septal nuclei.     

Thalamic connections with limbic cortex. II. Corticothalamic projections

The corticothalamic projections from the cat limbic cortex have been investigated with anterograde and retrograde axonal transport techniques. Five limbic cortical areas—the anterior limbic area, the cingular area, the granular and dysgranular retrosplenial areas, and the presubiculum—were identified on the basis of their cytoarchitecture. Emphasis was placed on determining the laminar distribution of the cells of origin of the efferent projections, the projection pathways, and the sites of termination within the thalamus. Projections to the thalamus originate in layers V and VI of limbic cortex. In the cingular region the cells of origin are predominantly in layer V and to a lesser extent in layer VI, while the majority of cells projecting from the more caudal retrosplenial areas and presubiculum are in layer VI. There are two fiber pathways from each cortical area to the thalamus. One system of fibers passes through the internal capsule and lateral thalamic peduncle, and a second system travels in the cingulate fasciculus before piercing the corpus callosum to join the postcommissural fornix. The lateral dorsal nucleus and the anterior nuclear group, including the anterior dorsal, anterior ventral, and anterior medial nuclei, are the major thalamic recipients of projections from limbic cortex. Corticothalamic projections also terminate sparsely in the midline and intralaminar nuclear complex, including the central lateral, central dorsal, paracentral, central medial, rhomboid, and reuniens nuclei. Projections from the anterior limbic area project predominantly to the anterior medial, centrall lateral, and paracentral nuclei. The anterior ventral nucleus, anterior medial nucleus, and lateral dorsal nucleus are the major thalamic recipients of projections from the cingular area, the granular and dysgranular retro-splenial areas, and the presubiculum. It appears that the anterior dorsal nucleus receives afferents only from the dysgranular retrosplenial area. Bilateral corticothalamic projections were found in the anterior medial, dorsal medial, central lateral, central medial, paracentral, and reuniens nuclei.     

Kindling induces neuropsin mRNA in the mouse brain

Neuropsin mRNA expression was analyzed and mapped in the mouse brains after kindling epileptogenesis by using in situ hybridization histochemistry. Dynamic increases of the neuropsin mRNA were observed in the layer II of prelimbic, somatosensory, auditory, perirhinal, entorhinal, and piriform cortices in an activity-dependent manner, though no neuropsin gene was expressed in these areas in control mice. In addition to the confirmation of our previous studies showing increases of mRNA in the hippocampus and amygdaloid complex, there were also remarkable increases of the neuropsin mRNA in the limbic areas, such as the accessory olfactory nucleus, the medial and lateral septal nucleus, the nucleus of diagonal band, the substantia innominata and the zona incerta. The dynamic activity-dependent changes of the gene expression and the site-specificity of neuropsin localization are suggesting that this molecule is implicated in cortical- and limbic-specific neuronal reorganization.     

An analysis of the efferent connections of the septal area in the cat

The neuroanatomical organization of the efferent connections of the septal area in the cat was analyzed by the use of anterograde ([3H]leucine radioautography) and retrograde (horseradish peroxidase histochemistry) tracing techniques. The results indicate that the lateral septal nucleus projects to the nuclei of the diagonal band, preoptic area, lateral hypothalamus, and supramammillary region. The projections of the septofimbrial nucleus supply the nuclei of the diagonal band and the medial habenular nucleus. Projection targets of the vertical limb of the diagonal band are widespread and include the preoptic area, lateral hypothalamus, anterior limbic cortex, amygdala, medial habenular nucleus, interpeduncular nucleus and hippocampal formation. The projection from the vertical limb to the hippocampal formation is organized in a topographical manner in such a fashion that cells positioned near the midline project to the dorsal hippocampus and adjoining subicular cortex while fibers originating from cells situated more laterally project to more ventral parts of the hippocampal formation. In general, the projections from the horizontal limb were similar to those from the vertical limb, but several differences were noted. Fibers arising from the horizontal limb are distributed to the ventral tegmental area and interpeduncular nucleus but this region seems to lack a projection to either the habenular complex or to the ventral aspect of the hippocampal formation. Fibers arising from the bed nucleus of the anterior commissure are distributed to the preoptic region, lateral hypothalamus, supramammillary region, posterior aspect of the medial mammillary nucleus and lateral habenular nucleus.     

Distribution of corticotropin-releasing factor mRNA and immunoreactivity in the central auditory system of the rat.

Hybridization histochemical and immunohistochemical methods were used to characterize the distribution of corticotropin-releasing factor (CRF) messenger RNA (mRNA) and peptide, respectively, in the central auditory system of the rat. Cell bodies expressing CRF mRNA and/or immunoreactivity (IR) were detected at each level of the system, including sparse or equivocal localizations in the dorsal cochlear nucleus, the medial nucleus of the trapezoid body, and the lateral superior olive. More prominent groups of cells expressing CRF mRNA and CRF-IR were found in the nuclei of the lateral lemniscus, the shell of the inferior colliculus, the medial division of the medial geniculate body and in primary auditory cortices. The latter showed the greatest density of CRF-expressing interneurons, distributed primarily in layers II, III and V, of any neocortical area. Results obtained using the two staining methods were in good agreement, except in the cochlear and superior olivary nuclei, where cells displaying CRF-IR were apparent in far greater abundance than those expressing CRF mRNA. CRF-IR fibers and terminals were detected in regions generally consistent with the cellular localizations described above. These results provide evidence for a surprisingly widespread expression of CRF in the auditory system of the rat. This includes generally low levels of expression in components of the primary auditory path (cochlear nucleus, trapezoid body, superior olive, lemniscal nuclei). CRF appears to be more prominently expressed in so-called non-primary components of the auditory system, including aspects of the medial geniculate body that constitute an interface between the auditory system and stress-related limbic system circuitry.     

Efferent projections of infralimbic and prelimbic areas of the medial prefrontal cortex in the Japanese monkey, Macaca fuscata

The infralimbic area (IL) and prelimbic area (PL) have been postulated as an autonomic motor region in the medial prefrontal cortex. The present study was conducted to reveal the projection sites of IL and PL of the monkey, Macaca fuscata, using biotinylated dextran amine as an anterograde tracer. IL and PL projected densely to the ventromedial caudate nucleus, the core and shell of the nucleus accumbens (Acb), parvicellular lateral basal and magnocellular accessory basal nuclei of the amygdala, lateral preoptic area, ventromedial hypothalamic nucleus, tubero-mammillary nucleus (TM), medial part of the magnocellular and dorsal part of the parvicellular (MDpc) dorsomedial thalamic nuclei, reunience and medial part of the medial pulvinar nucleus, and dorso-lateral part of the periaqueductal gray (PAGdl) in the mesencephalon. Moderately to weakly projected areas were the intermediate and lateral parts of the agranular insular cortex, orbital part of area 12, agranular and dysgranular part of the temporal pole cortex (TPa-g), auditory temporal cortex, lateral and medial (MS) septal nuclei, bed nucleus of the stria terminalis, diagonal band of Broca, substantia innominata, and medial preoptic area, dorsomedial, lateral, and posterior hypothalamic nuclei, magnocellular lateral basal and lateral amygdaloid nuclei, paratenial, paraventricular (PV), inter-antero-medial (IAM), reticular, central medial (CeM), parafascicular (PF) and limitans nuclei of the thalamus, lateral habenular nucleus, pedunculo-pontine nucleus, dorsal part of the lateral lemniscal nucleus, ventral tegmental area (VTA), dorsal raphe, superior central nucleus, medial and lateral parabrachial nuclei (PBl) and nucleus locus coeruleus (LC). A few scattered terminals were observed in the perifornical nucleus of the hypothalamus and substantia nigra pars compacta. PL and area 24 were characterized by projections to the entorhinal (Ent) and piriform (Pir) cortex as well as to the magnocellular part of the ventral anterior thalamic nucleus (VAmc). The morphology of the terminal arborization in each nuclei was different in appearance, perhaps reflecting the synaptic interaction between the nerve terminals and postsynaptic dendrites. PL projected uniquely to Ent, Pir and VAmc and IL projected uniquely to TPa-g, MS, IAM, CeM, MDpc, PF, PBl and LC. IL projected more strongly than PL to the shell of Acb, amygdaloid nuclei, PV, TM, VTA and PAGdl. The present results support the hypothesis that IL is a major cortical autonomic motor area and PL integrates limbic and autonomic inputs in the primate.     

Efferent projections of infralimbic and prelimbic areas of the medial prefrontal cortex in the Japanese monkey, Macaca fuscata

The infralimbic area (IL) and prelimbic area (PL) have been postulated as an autonomic motor region in the medial prefrontal cortex. The present study was conducted to reveal the projection sites of IL and PL of the monkey, Macaca fuscata, using biotinylated dextran amine as an anterograde tracer. IL and PL projected densely to the ventromedial caudate nucleus, the core and shell of the nucleus accumbens (Acb), parvicellular lateral basal and magnocellular accessory basal nuclei of the amygdala, lateral preoptic area, ventromedial hypothalamic nucleus, tubero-mammillary nucleus (TM), medial part of the magnocellular and dorsal part of the parvicellular (MDpc) dorsomedial thalamic nuclei, reunience and medial part of the medial pulvinar nucleus, and dorso-lateral part of the periaqueductal gray (PAGdl) in the mesencephalon. Moderately to weakly projected areas were the intermediate and lateral parts of the agranular insular cortex, orbital part of area 12, agranular and dysgranular part of the temporal pole cortex (TPa-g), auditory temporal cortex, lateral and medial (MS) septal nuclei, bed nucleus of the stria terminalis, diagonal band of Broca, substantia innominata, and medial preoptic area, dorsomedial, lateral, and posterior hypothalamic nuclei, magnocellular lateral basal and lateral amygdaloid nuclei, paratenial, paraventricular (PV), inter-antero-medial (IAM), reticular, central medial (CeM), parafascicular (PF) and limitans nuclei of the thalamus, lateral habenular nucleus, pedunculo-pontine nucleus, dorsal part of the lateral lemniscal nucleus, ventral tegmental area (VTA), dorsal raphe, superior central nucleus, medial and lateral parabrachial nuclei (PBl) and nucleus locus coeruleus (LC). A few scattered terminals were observed in the perifornical nucleus of the hypothalamus and substantia nigra pars compacta. PL and area 24 were characterized by projections to the entorhinal (Ent) and piriform (Pir) cortex as well as to the magnocellular part of the ventral anterior thalamic nucleus (VAmc). The morphology of the terminal arborization in each nuclei was different in appearance, perhaps reflecting the synaptic interaction between the nerve terminals and postsynaptic dendrites. PL projected uniquely to Ent, Pir and VAmc and IL projected uniquely to TPa-g, MS, IAM, CeM, MDpc, PF, PBl and LC. IL projected more strongly than PL to the shell of Acb, amygdaloid nuclei, PV, TM, VTA and PAGdl. The present results support the hypothesis that IL is a major cortical autonomic motor area and PL integrates limbic and autonomic inputs in the primate.     

Direct projections from the non-laminated divisions of the medial geniculate nucleus to the temporal polar cortex and amygdala in the cat

The medial geniculate nucleus (MG) is well known to send projection fibers not only to the auditory cortex, but also to the limbic structures of the forebrain including the perirhinal cortex and amygdala. In the cat, the non-laminated portions of the MG are also known to project to the amygdala, as well as to the auditory cortical areas surrounding the primary auditory area. On the other hand, projections from the non-laminated MG to the limbic cortical areas have not so far been studied systematically. Thus, in the present study, direct projections from the non-laminated portions of the medial geniculate nucleus to the temporal polar cortex and amygdala were examined in the cat by retrograde and anterograde tract-tracing techniques. The temporal polar cortex is the ventral polar region of the posterior sylvian and posterior ectosylvian gyri, which is located dorsal to the posterior rhinal sulcus and includes the ectorhinal area. After injection of cholera toxin B subunit into the temporal polar cortex, retrogradely labeled neurons were seen in the caudal two-thirds of the medial geniculate nucleus ipsilateral to the injection; they were distributed in the non-laminated portions of the MG (the dorsal and medial divisions and the ventromedial part of the ventral division), but not in the laminated portion (the principal part of the ventral division). These findings were confirmed by injecting Phaseolus vulgaris leucoagglutinin into each division of the MG. After the injection into each non-laminated division, terminal labeling was observed in the temporal polar cortex. Terminal labeling was further found in the lateral amygdaloid nucleus ipsilateral to the injection. Then, cholera toxin B subunit was injected into the lateral amygdaloid nucleus; retrogradely labeled neurons were observed ipsilaterally in the non-laminated portions of the MG, as well as in the temporal polar cortex. The results indicate that the non-laminated portions of the MG send projection fibers to the temporal polar cortex and lateral amygdaloid nucleus, and that the non-laminated portions of the MG and temporal polar cortex give rise to overlapping projections to the lateral amygdaloid nucleus. These connections appear to constitute neuronal links in “emotional” and/or “motivational” circuitry in the forebrain. © Wiley-Liss, Inc.     

Multiple single units and population responses during inhibitory gating of hippocampal auditory response in freely-moving rats

Paired clicks were presented to awake, freely-moving rats to examine neuronal activity associated with inhibitory gating of responses to repeated auditory stimuli. The rats had bundles of eight microwires implanted into each of four different brain areas: CA3 region of the hippocampus, medial septal nucleus, brainstem reticular nucleus, and the auditory cortex. Single-unit recordings from each wire were made while the local auditory-evoked potential was also recorded. The response to a conditioning stimulus was compared to the response to a test stimulus delivered 500 ms later: the ratio of the test response to the conditioning response provided a measure of inhibitory gating. Auditory-evoked potentials were recorded at all sites. Overall, brainstem reticular nucleus neurons showed the greatest gating of local auditory-evoked potentials, while the auditory cortex showed the least. However, except for the auditory cortex, both gating and non-gating of the evoked response were recorded at various times in all brain regions. Gating of the hippocampal response was significantly correlated with gating in the medial septal nucleus and brainstem reticular nucleus, but not the auditory cortex. Single-unit neuron firing in response to the clicks was most pronounced in the brainstem reticular nucleus and the medial septal nucleus, while relatively few neurons responded in the CA3 region of the hippocampus and the auditory cortex. Taken together, these data support the hypothesis that inhibitory gating of the auditory-evoked response originates in the non-lemniscal pathway and not in cortical areas of the rat brain.     

Thalamic connections with limbic cortex. I. Thalamocortical projections

The thalamocortical projections to limbic cortex in the cat have been studied with retrograde and anterograde axonal transport techniques. Five limbic cortical areas were identified on the basis of cytoarchitecture. The five areas are the anterior limbic area, the cingular area, the dorsal and ventral retrosplenial areas, and the presubiculum. Each of these cortical areas received small injections of horseradish peroxidase, and the afferent thalamic nuclei were identified by retrograde labelling of cells. The cortical projection of each of the anterior thalamic nuclei and the lateral dorsal nucleus was determined autoradiographically. Each of the anterior thalamic nuclei and the lateral dorsal nucleus projects to limbic cortex by two pathways. One group of fibers leaves the rostral thalamus by the fornix, pierces the corpus callosum, and joins the cingulate fasciculus to reach limbic cortex. The other group travels through the lateral thalamic peduncle and internal capsule. The anterior ventral nucleus projects primarily to the dorsal retroslenial area, particularly to layer I, the deep portion of layer II, and superficial portion of layer III. Sparse projections also exist to the ventral retrosplenial area, the cingular area, and the presubiculum. Very sparse projections to the anterior limbic area are seen. The anterior dorsal nucleus projects primarily to the ventral retrosplenial area, particularly layers I, the deep portion of layer II, and superficial layer III. Sparse projections exist to the dorsal retrosplenial area and presubiculum, but apparently no projections exist to the cingular or anterior limbic area. The anterior medial nucleus projects primarily to layers I and superficial III of the ventral retrosplenial area. Sparse projections exist to each of the other limbic cortical areas. The lateral dorsal nucleus projects extensively onto limbic cortex. Prominent projections occur to layer I, the external granular layer and lamina dessicans of the presubiculum, layers I and III-IV of the dorsal retrosplenial area, and layers I, III, and IV of the cingular area. Sparse projections occur to the ventral retrosplenial area and the anterior limbic areas. Thalamocortical projections also originate in the midline and intralaminar nuclei including the central medial reuniens, rhomboid, paracentral, central lateral, and central dorsal nuclei. These data indicate that the anterior thalamic nuclei project upon limbic cortex in a complex manner. Further, the projections to limbic cortex from the anterior nuclei overlap with projections from the lateral dorsal nucleus. This overlap of thalamic projections onto limbic cortex suggests a convergence of information from nonprimary sensory systems with information from the classical limbic system.