Role of the anterodorsal and anteroventral nuclei of the thalamus in spatial memory in the rat

This study tests the hypothesis that the anterior thalamic nuclei play a significant role in spatial learning and memory. Adult, male Sprague-Dawley rats with bilateral ibotenic acid lesions of the anterior thalamus were tested for 5 days in a repeated acquisition water maze task. Compared with Controls, rats with nearly complete lesions of both anterodorsal (AD) and anteroventral (AV) thalamic nuclei (AD/AV) were only mildly impaired in their spatial learning and memory. Larger lesions that extended into the anteromedial (AM) thalamic nucleus (AD/AV+) caused a more severe impairment and complete lesions of all three anterior nuclei (AD/AV/AM) resulted in even greater impairment that extended to all aspects of the task. In probe trials, only the Control animals had a preference for the correct quadrant. Approximately one-half of the rats were tested for a second week to determine if the impaired groups would benefit from further training. AD/AV/AM rats showed little improvement, but the other groups all improved significantly in all aspects of the task except the probe trial. Together, these data indicate that the anterior thalamic nuclei contribute to spatial learning and memory, but neither AV nor AD independently plays a dominant role.     

Topographic organization of subcortical projections to the anterior thalamic nuclei in the rat.

Subcortical projections to the anterior thalamic nuclei were studied in the rat, with special reference to projections from the mammillary nuclei, by retrograde and anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase. The medial mammillary nucleus (MM) projects predominantly ipsilaterally to the entire anterior thalamic nuclei, whereas the lateral mammillary nucleus projects bilaterally to the anterodorsal nucleus (AD) of the anterior thalamic nuclei. A topographic relationship was recognized between the MM and the anterior thalamic nuclei. The dorsal region of the pars mediana of the MM projects to the interanteromedial nucleus (IAM), whereas the ventral region projects to the rostral part of the anteromedial nucleus (AM). The dorsal and the ventral regions of the pars medialis project to the dorsomedial part of the AM at its caudal and rostral levels, respectively. The dorsomedial region of the pars lateralis projects to the ventral AM. The ventrolateral region of the pars lateralis projects to the ventral part of the anteroventral nucleus (AV) in such a manner that rostral cells project rostrally and caudal cells project caudally. The pars basalis projects predominantly ipsilaterally to the dorsolateral AV and bilaterally to the AD. The rostrolateral region of the pars posterior projects to the lateral AV, whereas the medial and the caudal regions of the pars posterior project to the dorsomedial AV. The rostrodorsal part of the nucleus reticularis thalami was found to project to the anterior thalamic nuclei; cells located rostrally in this part project to the IAM and AM, whereas cells located caudodorsally project to the AV and AD. The laterodorsal tegmental nucleus projects predominantly ipsilaterally to the AV, especially to its dorsolateral part. The present study demonstrates that subdivisions of the subcortical structures are connected to the subnuclei of the anterior thalamic nuclei, with a clear-cut topography arranged in the dorsoventral and the rostrocaudal dimensions.     

Projections from the anterodorsal and anteroveniral nucleus of the thalamus to the limbic cortex in the rat

The present study characterized the projections of the anterodorsal (AD) and the anteroventral (AV) thalamic nuclei to the limbic cortex. Both AD and AV project to the full extent of the retrosplenial granular cortex in a topographic pattern. Neurons in caudal parts of both nuclei project to rostral retrosplenial cortex, and neurons in rostral parts of both nuclei project to caudal retrosplenial cortpx. Within AV, the magnocellular neurons project primarily to the retrosplenial granular a cortex, whereas the parvicellular neurons project mainly to the retrosplenial granular b cortex. AD projections to retrosplenial cortex terminate in very different patternsthan do AV projections: The AD projection terminates with equal density in layers I, III, and IV of the retrosplenial granular cortex, whereas, in contrast, the AV projections terminate very densely in layer Ia and less densely in layer IV. Further, both AD and AV project densely to the postsubicular, presubicular, and parasubicular cortices and lightly to the entorhinal (only the most caudal part) cortex and to the subiculum proper (only the most septal part). Rostral parts of AD project equally to all three subicular cortices, whereas neurons in caudal AD project primarily to the postsubicular cortex. Compared to AD, neurons in AV have a less extensive projection to the subicular cortex, and this projection terminates primarily in the postsubicular and presubicular cortices. Further, the AD projection terminates in layers I, II/III, and V of postsubiculum, whereas the AV projection terminates only in layers I and V. © 1995 Wiley-Liss, Inc.     

Thalamic projections to retrosplenial cortex in the rat

The topographic relationships between anterior thalamic neurons and their terminal projection fields in the retrosplenial cortex of the rat were characterized by experiments with the fluorescent dye retrograde labeling technique. The results demonstrate that the anterodorsal (DAD) and anteroventral (AV) nuclei project heavily to retrosplenial granular cortex (Rg) and to a lesser extent to retrosplenial agranular cortex (Rag). In contrast, the anteromedial (AM) and lateral dorsal (LD) nuclei project heavily to Rag and more lightly to Rg. Irrespective of terminal field in Rg or Rag, the neuronal cell bodies in AD and AV are organized topographically so that the neurons in the caudal part of each nucleus project to rostral retrosplenial cortex and the neurons in the rostral portion of each nucleus project to the caudal retrosplenial cortex. Further, the ventromedial AD and AV neurons project to rostral retrosplenial cortex, whereas dorsolateral neurons in both nuclei project to caudal retrosplenial cortex. LD neurons display a different topographic organization. The neurons in the medioventral part of LD project primarily to the rostral retrosplenial cortex, and the neurons in lateral LD project to the caudal retrosplenial cortex. This latter projection to the caudal retrosplenial cortex is also contributed to by neurons residing in the mediodorsal part of caudal LD. The neurons in AM that project to the retrosplenial cortex display less segregation than the AV, AD, or LD neurons. In all experiments, a number of neurons in the dorsal ventro-anterolateral nucleus were labeled by retrosplenial injections. The largest number of cells in this nucleus were labeled after Rag injections, and these were topographically organized such that the neurons projecting to the rostral Rag were located immediately deep to the internal medullary lamina, and the neurons projecting to the caudal Rag were more ventrally located. Very few thalamic neurons have axon collaterals to different areas of the retrosplenial cortex as shown by double labeling experiments. Together, these results demonstrate a highly organized thalamic projection to the retrosplenial cortex.     

Chemical parcellation of the anterior thalamic nuclei in the human brain

The anterior thalamic nuclei (ATN) encompass a large region of the anteromedial aspect of the human thalamus. Three ATN have been classically described: anteroventral (AV), anteromedial (AM) and anterodorsal (AD). The present study has carried out histochemical and immunohistochemical procedures in the ATN of normal individuals to analyze whether these nuclei are chemically distinct. The markers used in this study were acetylcholinesterase (AChE), limbic system-associated membrane protein (LAMP), the calcium binding proteins calbindin D-28k (CB), parvalbumin (PV), and calretinin (CR), and the neuropeptides substance P (SP) and enkephalin (ENK). Other cytoarchitectural and myeloarchitectural techniques, specifically Nissl and Gallyas stainings, were used to delineate the boundaries of the ATN. The main findings of this study are: 1) AChE was very abundant in the AD and was irregular or heterogeneously distributed in the AV and AM; 2) LAMP immunoreactive (ir) neuropil was present throughout the ATN and its distribution was heterogeneous in the AV and AM; 3) the ATN harbored CB-, PV- and CR-ir neurons and neuropil; and, 4) the neuropeptide analysis revealed numerous SP positive varicose fibers scattered throughout the ATN in contrast to very few ENK-ir varicose fibers. These morphological findings describe a heterogeneous chemical anatomy in the human ATN which may reflect regional differences in the functional organization of the ATN with respect to the other thalamic nuclei and the cerebral cortex.     

Lesions of the tissue surrounding the preoptic recess (AV3V region) affect neurosecretory cells in the paraventricular nuclei in the rat

Lesions of the tissue surrounding the preoptic recess (AV3V region) have severe effects on body fluid homeostasis; these include acute adipsia and failure of the antidiuretic response. Because neurosecretory cells in supraoptic nuclei comprise the major source of antidiuretic hormone (ADH) in this species, we have previously observed the fine structure of supraoptic nuclei in rats with AV3V lesions. Paraventricular nuclei are the other major source of ADH in rats. Therefore, in this investigation we compared the fine structure of paraventricular nuclei in rats which had received AV3V lesions 3 days earlier with that of control rats which had received sham lesions and either had drinking water available or had water withheld for 3 days. Degenerating axons and axon terminals were present in paraventricular nuclei of lesioned rats. The degenerating terminals were in axodendritic and less often in axosomatic synapses. Morphometric evaluation revealed that neurosecretory cells did respond to the dehydrated state of the adipsic-lesioned animals, but the response was significantly attenuated compared to that which occurred in sham-lesioned rats deprived of water for 3 days. It appears that AV3V lesions damage afferent connections and impair the response of neurosecretory cells to dehydration in paraventricular as well as supraoptic nuclei. However, in paraventricular nuclei the response is not completely prevented by AV3V lesions during the adipsic period as was observed in supraoptic nuclei. The presence of a response in paraventricular nuclei may be at least partially stimulated by reduced body fluid volume. Information from volume receptors would be carried from the medulla to paraventricular nuclei by ascending pathways which are not affected by AV3V lesions.     

Distribution of 'non-specific' cholinesterase histochemical staining in the dorsal thalamus: a comparative study in rodents

Histochemical studies in rat dorsal thalamus demonstrate that 'non-specific' cholinesterase (ChE) enzyme activity is characteristic of neurons of the anterior dorsal (AD) and reuniens (Re) nuclei and in a cell group found as part of the central lateral (CL) and lateral dorsal (LD) nuclei. Extra-somatal ChE staining also is seen in the anterior ventral (AV) nucleus. Parallel histochemical studies in other rodents reveal slight ChE activity in neurons of the mouse AD and LD, but not in other thalamic nuclei. The dorsal thalami of hamsters, gerbils and guinea pigs show no detectable cellular staining of ChE, although low levels of extra-somatal ChE appear in AV and the internal medullary lamina. These data indicate that 'non-specific' cholinesterase activity is not found commonly in neurons of the dorsal thalamus and prominent ChE staining may be unique to the laboratory rat.     

Distribution of ‘non-specific’ cholinesterase histochemical staining in the dorsal thalamus: a comparative study in rodents

Histochemical studies in rat dorsal thalamus demonstrate that ‘non-specific’ cholinesterase (ChE) enzyme activity is characteristic of neurons of the anterior dorsal (AD) and reuniens (Re) nuclei and in a cell group fouund as part of the central lateral (CL) and lateral dorsal (LD) nuclei. Extra-somatal ChE staining also is seen in the anterior ventral (AV) nucleus. Parallel histochemical studies in other rodents reveal slight ChE activity in neurons of the mouse AD and LD, but not in other thalamic nuclei. The dorsal thalami of hamsters, gerbils and guinea pigs show no detectable cellular staining of ChE, although low levels of extra-somatal ChE appear in AV and the internal medullary lamina. These data indicate that ‘non-specific’ cholinesterase activity is not found commonly in neurons of the dorsal thalamus and prominent ChE staining may be unique to the laboratory rat.     

Cingulate cortex of the rhesus monkey: I. Cytoarchitecture and thalamic afferents

The cytoarchitecture and thalamic afferents of cingulate cortex were evaluated in the rhesus monkey (Macaca mulatta). Area 24 has three divisions of which area 24a is adjacent to the callosal sulcus and has the least laminar differentiation. Area 24b has more clearly defined layers II, III, and Va, and area 24c, which forms the lower bank of the anterior cingulate sulcus, has a particularly dense layer III. Area 23 also has three divisions, each of which has a distinct layer IV. Area 23a is adjacent to the callosal sulcus and has the thinnest layers II-IV, which have the same cell density as layers V and VI. Area 23b has the largest pyramids in layers IIIc and Va, and area 23c, in the depths of the posterior cingulate sulcus, has the broadest external and thinnest internal pyramidal layers. Finally, areas 29 and 30 are located in the posterior depths of the callosal sulcus. Two divisions of area 29 are apparent: one with a granular layer directly adjacent to layer I (area 29a-c) and another with differentiation of layers III and IV (area 29d). Area 30 has a dysgranular layer IV. Injections of the retrograde tracer horseradish peroxidase (HRP) were made into subdivisions of cingulate cortex in the monkey. Area 25 received thalamic input mainly from the midline parataenial (Pt), central densocellular (Cdc), and reuniens nuclei as well as from the dorsal parvicellular division of the mediodorsal nucleus (MDpc). A less dense projection also originated in the intralaminar parafascicular (Pf), central superior, and limitans (Li) nuclei as well as the medial division of the anterior nuclei (AM). Areas 24a and 24b received most thalamic afferents from fusiform and multipolar cells in the Cdc and Pf nuclei with fewer from the ventral anterior (VA) and MDpc and MD densocellular (MDdc) nuclei and only minor input from AM. Most input to premotor cingulate area 24c appeared to originate in VA, MDdc, and Li. Area 29 received the most dense input from nuclei traditionally associated with limbic cortex including the anteroventral (AV), anterodorsal (AD), and laterodorsal (LD) nuclei. Areas 23a and 23b, in contrast, did not receive AV, AD, or LD input, but the greatest proportion of their thalamic afferents arose in AM. Less-pronounced input also came from the lateroposterior (LP), medial pulvinar, and MDdc nuclei.(ABSTRACT TRUNCATED AT 400 WORDS)     

Connections of the retrosplenial granular a cortex in the rat

Although the retrosplenial granular a cortex (Rga) is situated in a critical position between the hippocampal formation and the neocortex, few studies have examined its connections. The present experiments use both retrograde and anterograde tracing techniques to characterize the afferent and efferent connections of Rga. Cortical projections to Rga originate in the ipsilateral area infraradiata, the retrosplenial agranular and granular b cortices, the ventral subiculum, and the contralateral Rga. Subcortical projections originate in the claustrum, the diagonal band of Broca, the thalamus, the midbrain raphe nuclei, and the locus coeruleus. The thalamic projections to Rga originate mainly in the anterodorsal (AD) and laterodorsal (LD) nuclei with sparse projections arising in the anteroventral (AV) and reuniens nuclei. Each projection to Rga terminates in distinct layers of the cortex. The thalamic projection from AD terminates primarily in layers I, III, and IV of Rga, whereas the axons arising from the LD nucleus have a dense terminal plexus only in layer 1. The projections arising from the subiculum end predominantly in layer II, whereas the postsubiculum projects to layers I and III-V. Axons from the contralateral Rga form a dense terminal plexus in layers IV and V, with a smaller number of terminals in layers I and VI. Rga projects ipsilaterally to the AV and LD nuclei of the thalamus and to the anterior cingulate, retrosplenial agranular,a and postsubicular cortices. Contralaterally it projects to the retrosplenial agranular and Rga cortices. Rga projections to the thalamus terminate ipsilaterally in the dorsal part of LD and bilaterally in AV. Together, these data suggest that Rga integrates thalamic with limbic information.     

Immunoelectron microscopic study of glutamate inputs from the retrosplenial granular cortex to identified thalamocortical projection neurons in the anterior thalamus of the rat

We have carried out an ultrastructural study to determine the characteristics and distribution of glutamate-containing constituents of the anterodorsal (AD) and anteroventral (AV) thalamic nuclei in adult rats. We used a polyclonal antibody to glutamate and a postembedding immunogold detection method in animals in which the neurons of AD/AV projecting to the cortex had been retrogradely labelled and the terminals of corticothalamic afferents anterogradely labelled by injection of cholera toxin-horseradish peroxidase (HRP) into the retrosplenial granular cortex. The heaviest immunogold labelling was over axon terminals 0.42 to 2.2 microm in diameter containing round synaptic vesicles and establishing Gray type 1 (asymmetric) synaptic contact (type 1 terminals) on HRP-labelled or non-labelled dendrites. Mean gold particle densities over such terminals were 3-4 times higher than the densities over the dendrites to which they were presynaptic and 5-6 times higher than over terminals establishing Gray type 2 (symmetric) synaptic contacts (type 2 terminals). Gold particle densities over neuronal cell bodies and dendrites and over a subpopulation of myelinated axons were intermediate between the densities over type 1 and type 2 terminals. In adjacent serial sections immunoreacted for gamma aminobutyric acid, type 2 terminals were heavily immunolabelled whereas type 1 terminals and other profiles with moderate gold particle densities after glutamate immunoreaction displayed very low labelling. A subpopulation of small type 1 axon terminals (up to 1 microm diameter) contained HRP reaction product identifying them as cortical in origin; they contacted small dendritic profiles (most <1 microm diameter) many of which also contained HRP reaction product. We conclude that terminals of the corticothalamic projection from retrosplenial granular cortex to AD/AV are glutamatergic and innervate predominantly distal dendrites of thalamocortical projection neurons.     

Long-term effects of lesions of the tissue surrounding the preoptic recess on paraventricular nuclei in rats

In this investigation we have observed the effects of withholding water for 5 days, the effects of long-term (5 weeks) lesions of the tissue surrounding the preoptic recess in the anteroventral third ventricle (AV3V region), and the interaction of the effects of long-term AV3V lesions and water deprivation on paraventricular nuclei. The purpose of these observations was to see if recovery of the antidiuretic response after AV3V lesions is associated with recovery of fine structural responses in these neurosecretory cells. Paraventricular neurosecretory cells of rats deprived of water for 5 days were hypertrophied in controls and in rats with AV3V lesions. Areas of cell bodies and their nuclei were increased, as were the number of Golgi stacks and electron dense (immature) neurosecretory granules. A greater percentage of nucleoli were adjacent to the nuclear envelope. Paraventricular neurons of rats with AV3V lesions also had fine structural changes characteristic of increased secretory activity, even in animals with free access to drinking water. The areas of cells and their nucleoli in coronal sections, and the number of Golgi stacks and electron-dense neurosecretory granules per cell were significantly increased in both treatment groups with AV3V lesions. There was a greater increase in the numbers of Golgi stacks and immature neurosecretory granules tended to be more numerous in water-deprived lesioned rats than in water-deprived controls. We suggest that recovery of body fluid balance in rats with chronic AV3V lesions involves enhanced secretory activity of neurosecretory cells in paraventricular nuclei, possibly stimulated via undamaged descending connections from the subfornical organ and by ascending pathways activated by cardiovascular volume receptors.     

Development of 'non-specific' cholinesterase-containing neurons in the dorsal thalamus of the rat

In adult rats, neurons displaying histochemical staining for 'non-specific' cholinesterase (ChE) are found 3 distinct regions of the dorsal thalamus: the thalamic reuniens nucleus (Re), the anterior dorsal nucleus (AD), and a region that includes the lateral part of the central lateral nucleus (CL) and the ventral portion of the lateral dorsal nucleus (LD). Normal development of ChE-positive neurons was studied with cholinesterase histochemical techniques in postnatal infant rats. Although ChE staining of capillary endothelium is detectable shortly after birth, ChE staining of neurons first occurs at about postnatal day 5 (PND 5) with light staining of AD and CL-LD. At PND 7, staining in AD and CL-LD has increased in intensity and staining also is present in neurons of the anterior ventral (AV) and ventral anterior (VA) nuclei. ChE staining of neurons in Re first appears at PND 10. The number of neurons staining for ChE in each of these nuclei, and also the intensity of staining in individual neurons, appear to increase during the next several days until about PND 14. After PND 14, ChE staining intensity in neurons of AD, Re, and CL-LD appears to plateau and the pattern of staining continues into adulthood. In contrast, ChE staining of neurons in VA declines markedly and only a very few neurons in the dorsal part of VA remain ChE-positive after PND 21. ChE staining of neuropil in AV increases markedly, obscuring somatal staining in this nucleus. These results are discussed in regard to transient and continued expression of ChE activity in the dorsal thalamus and possible functional roles of ChE.     

The effects of tranverse cuts caudal to the preoptic recess on the hypothalamo-neurohypophyseal neurosecretomy system

Electrolytic lesions of tissue surrounding the preoptic recess (AV3V region) appear to cause loss of stimulatory input to the supraoptic nuclei from angiotensin receptors and osmoreceptors. To investigate the pathways affected by AV3V lesions, we observed the ultrastructural effects of coronal cuts in a plane caudal to the organum vasculosum lamina terminalis upon supraoptic nuclei and neural lobes of rats. Like AV3V lesions, these cuts caused degeneration of axons and terminals in the supraoptic nuclei. Degenerating terminals lay in axodendritic synapses and in axosomatic synapses on neurosecretory cells. Unlike AV3V lesions, the cuts did not result in an appearance of decreased secretory activity in the supraoptic nuclei or decreased release of hormone from the neural lobe. On the contrary, terminals in the neural lobe tended to be depleted of neurosecretory material, and glial cell processes tended to be withdrawn from the secretory interface at the basal lamina surrounding fenestrated capillaries; both are changes which have been associated with enhanced hormone release. We suggest that inhibitory input to the supraoptic nuclei is lost as a result of these cuts.     

The effects of transverse cuts caudal to the preoptic recess on the fine structure of paraventricular nuclei in rats

Lesions of the tissue surrounding the preoptic recess (anteroventral third ventricle (AV3V) region) have been shown to severely impair normal mechanisms of body fluid homeostasis, including the antidiuretic response. In an earlier investigation of the pathways affected by these lesions, coronal cuts were placed between the level of the organum vasculosum lamina terminalis in the AV3V region and the level of the supraoptic nuclei. Rats with such cuts exhibited hyperdipsia and polyuria, but their plasma levels of antidiuretic hormone (ADH) were elevated. The fine structure of the supraoptic nucleus, a major site of ADH production, and of the neural lobe of the hypophysis, where ADH is released, were observed in rats with similar cuts. Although neural lobes showed evidence of hormone depletion and degenerating axons and terminals were present in supraoptic nuclei, there was no morphological evidence that neurosecretory cell bodies in supraoptic nuclei were affected by these cuts. Therefore, in this investigation we observed the ultrastructural effects of such cuts on paraventricular nuclei, which are the other major source of ADH. Degenerating axons and terminals were common in paraventricular nuclei of lesioned rats, both in the major magnocellular subnucleus and in the periventricular region. Cell bodies and nuclei of neurosecretory cells were not significantly larger in lesioned animals, but morphometric evaluations revealed dispersion of the Golgi complex and alterations in the rough endoplasmic reticulum of the cells. In addition, more multiple nucleoli were present, and nucleoli tended to lie adjacent to the nuclear envelope more frequently. We conclude that the neurosecretory cells in the paraventricular nuclei become more active in rats with these knife cuts.     

The postsubicular cortex in the rat: characterization of the fourth region of the subicular cortex and its connections.

The hippocampal formation contributes importantly to many cognitive functions, and therefore has been a focus of intense anatomical and physiological research. Most of this research has focused on the hippocampus proper and the fascia dentata, and much less attention has been given to the subicular cortex, the origin of most extrinsic projections from the hippocampal formation. The present experiments demonstrate that the postsubiculum is a distinct area of the subicular cortex. The major projections to the postsubiculum originate in the hippocampal formation, the cingulate cortex, and the thalamus (primarily from the anterodorsal (AD) nucleus and to a lesser extent from the anteroventral (AV) and lateral dorsal (LD) nuclei). These projections differ from the thalamic projections to presubiculum and parasubiculum. Efferent projections from the postsubiculum terminate in both cortical and subcortical areas. The cortical projections terminate in the subicular and retrosplenial cortices and in the caudal lateral entorhinal and perirhinal cortices. Subcortical projections primarily end in the AD and the LD nuclei of the thalamus. These thalamic projections end in areas that are distinct from those to which the presubiculum and parasubiculum project. For instance, the postsubiculum has a dense terminal field in the AD nucleus, but presubicular axons terminate predominantly in the AV nucleus. The cortical projections also distinguish postsubiculum. All subicular areas project to the entorhinal cortex, but the postsubicular projection ends in the deep layers (i.e. IV-VI), whereas presubiculum projects to layers I and III, and parasubiculum projects to layer II. Postsubiculum projects to retrosplenial granular b cortex and only incidentally to retrosplenial granular a cortex. In contrast presubiculum projects to the retrosplenial granular a cortex but not to the retrosplenial granular b cortex. These differences clearly mark the postsubiculum, the presubiculum, and the parasubiculum as distinct regions within the subicular cortex and suggest that they subserve different roles in the processing and integration of limbic system information.     

Lesion of the anteroventral third ventricle (AV3V) reduces hypothalamic activation and hypophyseal hormone secretion induced by lipopolysaccharide in rats

This study examined whether electrolytic ablation of the periventricular anteroventral third ventricle (AV3V) region would affect the hypothalamic activation and the increase of hypophysial hormone secretion induced by systemic injection of lipopolysaccharide (LPS) in rats. LPS significantly increased the number of cells showing Fos immunoreactivity in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus (P<0.05) and also increased plasma levels of vasopressin, oxytocin, adrenocorticotropin and corticosterone (P<0.05). AV3V lesion significantly reduced LPS-induced Fos immunoreactivity (P<0.05) and vasopressin and oxytocin secretion (P<0.05). Elevations in adrenocorticotropin but not in plasma corticosterone after LPS were affected by prior AV3V lesions. These findings demonstrate that LPS-induced Fos expression in the PVN and SON, and hypophysial hormone secretion is dependent on the integrity of the AV3V region.     

The distribution pattern of pathology and cholinergic deficits in amygdaloid complex in Alzheimer's disease and dementia with Lewy bodies

We studied the distribution pattern of pathology and cholinergic deficits in the subnuclei of the amygdaloid complex (AC) in five patients with Alzheimer's disease (AD), eight with dementia with Lewy bodies (DLB) and five normal controls. In controls, the basal nucleus contained the highest choline acetyltransferase activity; the activity in the lateral and central nuclei and those in the cortical, medial and accessory basal nuclei were comparable. In AD, there was a significant decrease in choline acetyltransferase activity in the accessory basal and lateral nuclei, in DLB a significant decrease was observed in the accessory basal, lateral and cortical nuclei. Compared to controls the hyperphosphorylated tau-pathology burden was significantly higher in the basal, central and medial nuclei in AD and in the central, cortical, lateral and medial nuclei in DLB. The amyloid plaque burden was significantly higher in the accessory basal, basal, lateral and cortical nuclei in AD and in all nuclei in DLB. The α-synuclein burden was significantly higher in all nuclei in both AD and DLB. Compared to AD α-synuclein burden was higher in all nuclei in DLB. There were no correlations between the distribution pattern of hyperphosphorylated tau-pathology, amyloid plaques and α-synuclein-positive structures, and choline acetyltransferase activity, except the lateral nucleus in DLB. In conclusion we found no relationship between the pattern of cholinergic deficits and the distribution pattern of lesions in the AC of patients with AD or DLB. Cholinergic deficits were more prominent in the nuclei of basolateral (BL) group in AD, whereas the nuclei of both BL and corticomedial groups were involved in DLB, which may be due to the involvement of both basal forebrain and brainstem cholinergic nuclei in the latter.     

Basal forebrain cholinergic and noncholinergic projections to the thalamus and brainstem in cats and monkeys

The projections of basal forebrain neurons to the thalamus and the brainstem were investigated in cats and primates by using retrograde transport techniques and choline acetyltransferase (ChAT) immunohistochemistry. In a first series of experiments, the lectin wheat germ-agglutinin conjugated with horseradish peroxidase (WGA-HRP) was injected into all major sensory, motor, intralaminar, and reticular (RE) thalamic nuclei of cats and into the mediodorsal (MD) and pulvinar-lateroposterior thalamic nuclei of macaque monkeys. In cats numerous neurons of the vertical and horizontal limbs of the diagonal band nucleus and the substantia innominata (SI), including its rostromedial portion termed the ventral pallidum (VP), were retrogradely labeled after WGA-HRP injections in the rostral pole of the RE complex, the MD, and anteroventral/anteromedial (AV/AM) thalamic nuclei. Fewer retrogradely labeled cells were observed in the same areas after injections in the ventromedial (VM) thalamic nucleus, and none or very few after other thalamic injections. After RE, MD, and AV/AM injections, 7-20% of all retrogradely labeled cells in the basal forebrain were also ChAT positive, while none of the retrogradely labeled neurons following VM injections displayed ChAT immunoreactivity. The basal forebrain projection to the MD nucleus was shown to arise principally from VP in both cats and macaque monkeys. In a second series of experiments performed in cats, injections of WGA-HRP in the brainstem peribrachial (PB) area comprising the pedunculopontine nucleus led to retrograde labeling of a moderate number of neurons in the lateral part of the VP, SI, and preoptic area (POA), only a few of which displayed ChAT immunoreactivity. In addition, a large number of retrogradely labeled cells were observed in the bed nuclei of the anterior commissure and stria terminalis after PB injections. In a third series of experiments, the use of the retrograde double-labeling method with fluorescent tracers in squirrel monkeys allowed us to identify a significant number of basal forebrain neurons sending axon collaterals to both the RE thalamic nucleus and PB brainstem area, while no double-labeled neurons were disclosed after injections confined to the ventral anterior/ventral lateral (VA/VL) thalamic nuclei and PB area or following injections in the cerebral cortex and PB area. Our findings reveal the existence of cholinergic and noncholinergic basal forebrain projections to the thalamus and the brainstem in both cats and macaque monkeys. We suggest that these projections may play a crucial role in the control of thalamic functions in mammals.     

Topographic organization of cortical and subcortical projections to posterior cingulate cortex in the cat: evidence for somatic, ocular, and complex subregions.

The posterior cingulate area (CGp) of the cat consists of cortex on the exposed cingulate gyrus and in the adjacent ventral bank of the splenial sulcus. We have placed deposits of distinguishable fluorescent tracers at multiple restricted sites in CGp and have analyzed the distribution throughout the forebrain of neurons labeled by retrograde transport. Cortical projections to CGp arise (in approximately descending order of strength) from anterior cingulate cortex; prefrontal cortex and premotor areas including the frontal eye fields; visual areas including especially areas 7 and 20b; parahippocampal areas; insular cortex; somesthetic areas; and auditory areas. Corticocortical pathways are organized topographically with respect to the posterior-anterior axis in CGp. Projections from prefrontal cortex and other areas with complex (as opposed to sensory, motor, or limbic) functions are concentrated posteriorly; projections from visual and oculomotor areas are concentrated at an intermediate level; and projections from areas with somesthetic and somatomotor functions are concentrated anteriorly. Thalamic projections to CGp arise from the anterior nuclei (AD, AV, and AM), from restricted portions of the ventral complex (VAd, VAm, and VMP), from discrete sectors of the lateral complex (LD, LPs, and LPm), from the rostral crescent of intralaminar nuclei (CM, PC, and CL), and from the reuniens nucleus. Projections from AM, VAd, LD, and LPs are spatially ordered in the sense that more ventral thalamic neurons project to more anterior cortical sites. Projections from AV and AD are stronger at more posterior cortical sites but do not show other signs of topographic ordering. Projections from LPm, CM, PC, CL, and RE are diffuse. We conclude (1) that cortical afferents of CGp derive predominantly from neocortical areas including those with well established sensory and motor functions; (2) that limbic projections to CGp originate primarily in structures, including the hippocampus, which are associated with memory, as opposed to structures, including the amygdala, which are associated with emotional and instinctual behavior; and (3) that CGp contains subregions in which complex, ocular, or somatic afferents predominate.