Structural basis for the functional specialization of the pallidal complex of the cat brain

Experiments carried out on 30 cats using retrograde axonal transport of markers (horseradish peroxidase and luminophores) were used to study the organization of the afferent projection system of the pallidal complex (the globus pallidum, the entopeduncular nucleus, the ventral pallidum) formed by fibers from functionally different cortical and subcortical structures (the ventral tegmental area, the substantia nigra, the amygdaloid boby). The distribution of afferent projection fibers in this complex of nuclei led to identification of the following zones: a “limbic” zone, corresponding to the ventral pallidum, and a “motor” zone, corresponding to the caudal part of the globus pallidum. On the one hand, the features of the afferent organization as demonstrated here can be regarded as a structural basis for the functional heterogeneity of the pallidal complex; on the other, significant regions within these structures (the rostral part of the globus pallidum and the entopeduncular nucleus) were found to receive projection fibers from functionally different structures, suggesting the existence of convergence and integration processes in these regions. Laboratory for the Physiology of Higher Nervous Activity, I. P. Pavlov Institute of Physiology, 199034 St. Petersburg. Translated from Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 82, No. 2, pp. 44–49, February, 1996.     

电刺激大鼠伏隔核对腹侧苍白球神经元自发放电的影响

目的:研究电刺激大鼠伏隔核(nucleus accumbens,NAC)对腹侧苍白球(ventral pallidum,VP)神经元放电的影响,探索电刺激NAC治疗药物成瘾的机制。方法:本实验应用细胞外记录方法观察不同频率电刺激(强度0.4mA,波宽0.06ms,时程5s,频率5,10,20,50,80,100,130,150和200Hz)大鼠NAC对VP神经元放电的影响。结果:刺激频率低于20Hz时,大多数VP神经元的放电频率无变化,电刺激频率大于20Hz可使大多数VP神经元的放电频率降低。结论:本研究提示高频刺激NAC对药物依赖可能有治疗作用。     

Projections of striatopallidal structures to the pedunculopontine nucleus of the tegmentum of the midbrain in dogs

A method based on retrograde axonal transport of horseradish peroxidase was used to study the striatopallidal afferent projections of the pendunculopontine nucleus of the midbrain (PPN) in dogs. The major source of these projections was found to be the pallidum, as both the compact and diffuse zones of this nucleus received projections from all of its structures: the entopeduncular nucleus, the globus pallidus, and the ventral pallidum. The striatal complex, specifically the nucleus accumbens, showed only occasional labeled neurons, projecting exclusively to the compact part of the PPN. Since the distribution of projection fibers arising from the functionally diverse territories of the striatopallidum and directed to individual structural subdivisions of the PPN showed no topical elements, identification of functionally specific (motor and limbic) areas of the PPN was not possible on the basis of the present analysis. __________ Translated from Morfologiya, Vol. 130, No. 6, pp. 30–34, November–December, 2006.     

An electrophysiological study of the neural projections from the hippocampus to the ventral pallidum and the subpallidal areas by way of the nucleus accumbens

The integrative role of the ventral striatum in transmitting signals from the hippocampus to the ventral pallidal and subpallidal areas was investigated in urethane-anaesthetized rats using an extracellular single-unit recording technique. Neurones of the nucleus accumbens were first activated by single-pulse stimulation of the ventral subiculum of the hippocampus. Further tests were made to investigate whether these accumbens neurones could be activated antidromically by stimulation of either the ventral pallidal or subpallidal areas. More than 4 times as many accumbens neurones, activated by hippocampal stimulation, responded antidromically to stimulation of subcommissural ventral pallidum than to stimulation of the sublenticular subpallidal area. This observation suggests that the hippocampus has preferential inputs to accumbens efferent neurones which project monosynaptically to the ventral pallidum. Spontaneously active neurones in the ventral pallidum and subpallidal area were inhibited by stimulation of the ventral subiculum of the hippocampus. These inhibitory responses were reduced when glutamic acid diethyl ester, a glutamate antagonist, was microinjected into the medial accumbens, apparently blocking the hippocampal-accumbens glutamatergic synapses to both the ventral pallidal-directed and the subpallidal-directed accumbens efferents. This evidence suggests that signals from the hippocampus reach ventral pallidal and subpallidal regions by way of the nucleus accumbens. The presence of a projection from ventral pallidal and subpallidal regions to the brainstem mesencephalic locomotor region further supports the hypothesis that limbic (e.g. hippocampus) can influence somatomotor activities by way of the nucleus accumbens and its efferent projection to ventral pallidal and subpallidal regions.     

Parvalbumin-immunoreactive neurons and GABAergic neurons of the basal forebrain project to the rat basolateral amygdala

The basal forebrain (BF) contains a diffuse array of cholinergic and non-cholinergic neurons that project to the cerebral cortex and basolateral nuclear complex of the amygdala (BLC). Previous studies have shown that the GABAergic subpopulation of non-cholinergic corticopetal BF neurons selectively innervates cortical interneurons. Although several investigations in both rodents and primates have indicated that some BF neurons projecting to the BLC are non-cholinergic, there have been no studies that have attempted to identify the neurochemical phenotype(s) of these neurons. The present study combined Fluorogold retrograde tract tracing with immunohistochemistry for two markers of BF GABAergic neurons, parvalbumin (PV) or glutamic acid decarboxylase (GAD), to determine if a subpopulation of BF GABAergic cells projects to the BLC. Injections of Fluorogold confined to the rat BLC, and centered in the basolateral nucleus, produced extensive retrograde labeling in the ventral pallidum and substantia innominata regions of the BF. Although the great majority of retrogradely labeled neurons were not double-labeled, about 10% of these neurons, located mainly along the ventral aspects of the fundus striati and globus pallidus, exhibited immunoreactivity for PV or GAD. The results of this investigation contradict the long-held belief that there is no extra-amygdalar source of GABAergic inputs to the BLC, and indicate that the cortex-like BLC, in addition to the cortex proper, receives inhibitory inputs from the basal forebrain.     

损毁Parkinson病大鼠腹侧苍白球对纹状体内多巴胺的影响

应用6羟基多巴胺(6OHDA)制备Parkinson病(PD)大鼠模型,插入电极通过直流电毁损腹侧苍白球(VP),观察毁损术后PD大鼠旋转行为的变化,并应用高压液相色谱检测纹状体内多巴胺(DA)及3,4二羟甲基苯丙氨酸(DOPAC)和去甲肾上腺素(NA)的含量。结果显示:直流电毁损VP可使PD模型大鼠的旋转行为明显减少;毁损侧纹状体内DA的含量减少,DOPAC和NA的含量增加。上述结果提示VP毁损可明显改善PD大鼠的旋转行为,此效应可能与抑制VP的异常兴奋有关。     

The role of the human globus pallidus in Huntington's disease

Huntington's disease (HD) is characterized by pronounced pathology of the basal ganglia, with numerous studies documenting the pattern of striatal neurodegeneration in the human brain. However, a principle target of striatal outflow, the globus pallidus (GP), has received limited attention in comparison, despite being a core component of the basal ganglia. The external segment (GPe) is a major output of the dorsal striatum, connecting widely to other basal ganglia nuclei via the indirect motor pathway. The internal segment (GPi) is a final output station of both the direct and indirect motor pathways of the basal ganglia. The ventral pallidum (VP), in contrast, is a primary output of the limbic ventral striatum. Currently, there is a lack of consensus in the literature regarding the extent of GPe and GPi neurodegeneration in HD, with a conflict between pallidal neurons being preserved, and pallidal neurons being lost. In addition, no current evidence considers the fate of the VP in HD, despite it being a key structure involved in reward and motivation. Understanding the involvement of these structures in HD will help to determine their involvement in basal ganglia pathway dysfunction in the disease. A clear understanding of the impact of striatal projection loss on the main neurons that receive striatal input, the pallidal neurons, will aid in the understanding of disease pathogenesis. In addition, a clearer picture of pallidal involvement in HD may contribute to providing a morphological basis to the considerable variability in the types of motor, behavioral, and cognitive symptoms in HD. This review aims to highlight the importance of the globus pallidus, a critical component of the cortical‐basal ganglia circuits, and its role in the pathogenesis of HD. This review also summarizes the current literature relating to human studies of the globus pallidus in HD.     

Efferent connections of the rostral linear nucleus of the ventral tegmental area in the rat

The ventral tegmental area (VTA) is crucially involved in brain reward, motivated behaviors, and drug addiction. This district is functionally heterogeneous, and studying the connections of its different parts may contribute to clarify the structural basis of intra-VTA functional specializations. Here, the efferents of the rostral linear nucleus (RLi), a midline VTA component, were traced in rats with the Phaseolus vulgaris leucoagglutinin (PHA-L) technique. The results show that the RLi heavily innervates the olfactory tubercle (mainly the polymorph layer) and the ventrolateral part of the ventral pallidum, but largely avoids the accumbens. The RLi also sends substantial projections to the magnocellular preoptic nucleus, lateral hypothalamus, central division of the mediodorsal thalamic nucleus, lateral part of the lateral habenula and supraoculomotor region, and light projections to the prefrontal cortex, basolateral amygdala, and dorsal raphe nucleus. A similar set of projections was observed after injections in rostromedial VTA districts adjacent to RLi, but these districts also send major outputs to the lateral ventral striatum. Overall, the data suggest that the RLi is a distinct VTA component in that it projects primarily to pallidal regions of the olfactory tubercle and to their diencephalic targets, the central division of the mediodorsal thalamic nucleus and the lateral part of the lateral habenula. Because the rat RLi reportedly contains a lower density of dopaminergic neurons as compared with most of the VTA, its unusual projections may reflect a non-dopaminergic, putative GABAergic, phenotype, and this distinctive cell population seemingly extends beyond RLi boundaries into the laterally adjacent VTA. By being connected to the central division of the mediodorsal thalamic nucleus (directly and via ventral striatopallidal system) and to the magnocellular preoptic nucleus, the RLi and its surroundings may play a role in olfactory-guided behaviors, which are part of the approach responses associated with appetitive motivational states.     

Effects of excitotoxic lesions in the ventral striatopallidal–thalamocortical pathway on odor reversal learning: inability to extinguish an incorrect response

The role of the ventral striatopallidal pathway and related cortical areas in stimulus-reward association reversal behavior was studied by inducing bilateral lesions with the excitotoxin, N-methyl-D-aspartate (NMDA) at restricted sites in the system. The areas lesioned were the ventral pallidum (VP), the ventral striatum (VS), the medial prefrontal cortex (mPFC) [i.e., the prelimbic (PL) and infralimbic (IL) cortexes], and the orbital cortex [i.e., the dorsolateral orbital (DLO), ventral lateral orbital (VLO), and lateral orbital (LO) cortexes]. Rats with lesions of the dorsal caudate nucleus and putamen (CPu) served as a positive control in this study. Water-deprived rats were trained on a go, no-go two-odor olfactory discrimination task to respond to one odor (S+) with water as a reward and to suppress responding to the other odor (S-). The rats were then tested for their ability to reverse the associated stimuli. The number of errors made before successfully learning the stimulus-reward association were measured in relation to a sham lesion control group which did not receive injections of NMDA. In experimental rats, the lesions did not affect their ability to learn stimulus-reward associations for novel odors, but did result in an increase in the number of false alarms after the significance of the associated stimuli were reversed. That is, the lesioned animals persisted in responding to the formerly rewarded but now unrewarded stimulus. Rats with damage to the CPu did not show a significant effect when compared with the controls during reversal problems. The results support the hypothesis that the ventral striatopallidal system, together with related thalamic and frontal cortical structures, functions in reversal learning by suppressing inappropriate responses to stimuli that are no longer rewarded.     

Convergent,not serial,striatal and pallidal circuits regulate opioid-induced food intake

Mu opioid receptor (MOR) signaling in the nucleus accumbens (NAcc) elicits marked increases in the consumption of palatable tastants. However, the mechanism and circuitry underlying this effect are not fully understood. Multiple downstream target regions have been implicated in mediating this effect but the role of the ventral pallidum (VP), a primary target of NAcc efferents, has not been well defined. To probe the mechanisms underlying increased consumption, we identified behavioral changes in rats' licking patterns following NAcc MOR stimulation. Because the temporal structure of licking reflects the physiological substrates modulating consumption, these measures provide a useful tool in dissecting the cause of increased consumption following NAcc MOR stimulation. Next, we used a combination of pharmacological inactivation and lesions to define the role of the VP in hyperphagia following infusion of the MOR-specific agonist [d-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO) into the NAcc. In agreement with previous studies, results from lick microstructure analysis suggest that NAcc MOR stimulation augments intake through a palatability-driven mechanism. Our results also demonstrate an important role for the VP in normal feeding behavior: pharmacological inactivation of the VP suppresses baseline and NAcc DAMGO-induced consumption. However, this interaction does not occur through a serial circuit requiring direct projections from the NAcc to the VP. Rather, our results indicate that NAcc and VP circuits converge on a common downstream target that regulates food intake.     

Spatial organization of the corticopalladial projection system of dog brain

Spatial organization of corticopallidal projectional system was studied in 11 outbred dogs by method based on horse radish peroxidase transport. It was demonstrated that globus pallidum receives projections predominantly from neocortical zones (motor, premotor, somatosensory, parietal and auditory and from insular field of mesocortex. Mesocortical (prelimbic, orbital and insular) and allocortical (entorhinal, piriform and periamygdalar) including archicortex (subicular part of hippocampal formations) fields project onto ventral pallidum. Entopeduncular nucleus receives projections from neocortical zones (motor, premotor, somatosensory, parietal and auditory), mesocortex (prelimbic, orbital, insular and cingular fields) and allocortex (entorhinal and periamygdalar fields). The data obtained indicate specificity of distribution of cortical afferent projectional fibres in each of nuclei studied which allows to consider globes pallidum as motor zone and ventral pallidum as limbic zone of paladial complex. As projections from functionally different cortical fields were revealed in entopeduncular nucleus it may be suggested that this is the exact site for interaction of functionally different information, including the one received from the cortex.     

Efferent connections of dorsal and ventral agranular insular cortex in the hamster, Mesocricetus auratus

The anterior portion of rodent agranular insular cortex consists of a ventral periallocortical region (AIv) and a dorsal proisocortical region (AId). Each of these two cortical areas has distinct efferent connections, but in certain brain areas their projection fields are partially or wholly overlapping. Bilateral projections to layers I, III and VI of medial frontal cortex originate in the dorsal agranular insular cortex and terminate in the prelimbic, anterior cingulate and medial precentral areas; those originating in ventral agranular insular cortex terminate in the medial orbital, infralimbic and prelimbic areas. The dorsal and ventral regions of the agranular insular cortex project topographically to the ipsilateral cortex bordering the rhinal fissure, which includes the posterior primary olfactory, posterior agranular insular, perirhinal and lateral entorhinal areas. Fibers to these lateral cortical areas were found to travel in a cell-free zone, between cortical layer VI and the claustrum, which corresponds to the extreme capsule. The dorsal and ventral regions send commissural projections to layer I, lamina dissecans and outer layer V, and layer VI of the contralateral homotopical cortex, via the corpus callosum. Projections from the ventral and dorsal regions of the agranular insular cortex to the caudatoputamen are topographically arranged and terminate in finger-like patches. The ventral, but not the dorsal region, projects to the ventral striatum and ventral pallidum. The thalamic projections of the ventral and dorsal regions are largely overlapping, with projections from both to the ipsilateral reticular nucleus and bilaterally to the rhomboid, mediodorsal, gelatinosus and ventromedial nuclei. The heaviest projection is that to the full anteroposterior extent of the medial segment of the mediodorsal nucleus. Brainstem areas receiving projections from the ventral and dorsal regions include the lateral hypothalamus, substantia nigra pars compacta, ventral tegmental area and dorsal raphe nucleus. In addition, the ventral region projects to the periaqueductal gray and the dorsal region projects to the parabrachial and ventral pontine nuclei.These efferent connections largely reciprocate the afferent connections of the ventral and dorsal agranular insular cortex, and provide further support for the concept that these regions are portions of an outer ring of limbic cortex which plays a critical role in the expression of motivated, species-typical behaviors.     

Organization of the efferent projections of the pedunculopontine tegmental nucleus of the midbrain of the dog pallidum

Studies of the pedunculopontinopallidal projections of the dog brain based on the retrograde axonal transport of horseradish peroxidase demonstrated that the compact zone (PPNc) and the lateral area of the diffuse zone (PPNd) of the pedunculopontine tegmental nucleus (PPN) of the midbrain project to the globus pallidus, entopeduncular nucleus, and ventral pallidum. The medial area of the PPNd, adjacent to the chiasm of the upper cerebellar peduncles and seen in other animals as the mesencephalic extrapyramidal area (MEA), projects only to the globus pallidus. In dogs, this area of the tegmentum is not a major source of projections to the striopallidum, such that it is inappropriate to regard it as a separate structure, comment being restricted to the topical organization of PPNd projections to the pallidum. Projection fibers to pallidal structures arise from both cholinergic and non-cholinergic PPN neurons. __________ Translated from Morfologiya, Vol. 127, No. 2, pp. 19–23, March–April, 2005.     

Comparative effects of quisqualic and ibotenic acid-induced lesions of the substantia innominata and globus pallidus on the acquisition of a conditional visual discrimination: differential effects on cholinergic mechanisms

Two experiments tested the hypothesis that the deficits in conditional discrimination learning produced by ibotenic acid-induced lesions of the ventral pallidum and substantia innominata are produced by loss of the magnocellular cholinergic cells in the nucleus basalis and adjacent regions. Experiment 1 replicated the previously reported deficit in conditional learning produced by ibotenate-induced lesions of the ventral pallidum/substantia innominata, but failed to demonstrate any restoration of learning by a subchronic regimen of the acetylcholinesterase inhibitor physostigmine sufficient to produce significant (30%), but equivalent, degrees of inhibition in the frontal cortex of ventral pallidum/substantia innominata-lesioned or sham-operated rats. Experiment 2 examined the effects of quisqualic acid-induced lesions of the ventral pallidum/substantia innominata. According to most of the measures of learning employed, the quisqualic acid-induced lesion of the ventral pallidum/substantia innominata failed to impair conditional learning, even though the quisqualate-induced lesion produced greater degrees of cholinergic neuron destruction than the ibotenate-induced lesion, as measured in terms of reductions in cortical choline acetyltransferase activity (44% vs 27%). Although consideration of individual data suggested that very high (60%) levels of choline acetyltransferase reduction in Experiment 2 might have detrimental effects of conditional learning, the overall failure of the quisqualate-induced lesions of the ventral pallidum/substantia innominata to impair learning is to be contrasted with the significant behavioural effects of ibotenate-induced lesions. Histological and immunocytochemical analysis showed that the quisqualate-induced lesion, unlike that produced by ibotenate, tended to produce less damage to the overlying dorsal globus pallidus and to parvocellular neurons of the ventral pallidum/substantia innominata, thus implicating these nonspecific effects of ibotenate-induced lesions in their behavioural effects. The present results question previous interpretations of the behavioural effects of ibotenate-induced lesions of the ventral pallidum/substantia innominata in terms of damage inflicted on the cortically-projecting cholinergic cells of the nucleus basalis, and suggest that quisqualic acid, although also nonspecific in its excitotoxic effects, is nevertheless more selective for producing damage to cholinergic neurons in the ventral pallidum/substantia innominata than ibotenic acid.     

Influence of ascending noradrenergic fibers on the neurotensin-like immunoreactive neurons in the rat paraventricular nucleus

The topographic organization of cells containing choline-acetyltransferase (CAT) and located within the magnocellular nuclei of the basal forebrain was studied by correlating maximum CAT decrease in one or another cortical region with a given localization of the cell lesions. Lesions were made by using ibotenic acid. Lesions affecting the ventral pallidum decreased CAT activity in the antero-medial prefrontal cortex and lesions of the internal and ventral borders of the pallidum decreased CAT activity in sensori-motor and parieto-temporal cortices. None of these lesions produced a decrease of CAT activity in the hippocampus. These results suggest that it is possible to show the presence of a specific cholinergic projection from the basal forebrain to the medial-associative prefrontal cortex of the rat.     

Integration and segregation of limbic cortico-striatal loops at the thalamic level: an experimental tracing study in rats

The frontal lobe and the basal ganglia are involved in a number of parallel, functionally segregated circuits. Information is thought to pass from distinct parts of the (pre)frontal cortex, via the striatum, the pallidum/substantia nigra and the thalamus, back to the premotor/prefrontal cortices. Currently, different views exist as to whether these circuits are to be considered as open or closed loops, as well as to the degree of interconnection between different circuits. The main goal of the present study is to answer some of these questions for the limbic corticostriatal circuits. The latter circuits involve the nucleus accumbens, the ventral pallidum/dorsomedial substantia nigra pars reticulata, the medial parts of the mediodorsal and ventromedial thalamic nuclei and the prefrontal cortex. Within the nucleus accumbens, a core and a shell region are recognized on the basis of anatomical and functional criteria. The shell of the nucleus accumbens projects predominantly to the mediodorsal, the midline and the reticular thalamic nuclei via the ventral pallidum, whereas the core reaches primarily the medial part of the ventromedial thalamic nucleus, the intralaminar and mediodorsal thalamic nuclei via a relay in the dorsomedial substantia nigra pars reticulata. By means of double labeling experiments with injections of anterograde tracers in both the ventral pallidum and the substantia nigra of rats, we were able to demonstrate that circuits involving the shell and the core of the nucleus accumbens remain largely segregated at the level of the thalamus. Only restricted areas of overlap of ventral pallidal and reticular nigral projections occur in the mediodorsal and ventromedial thalamic nuclei, which allows for a limited degree of integration, at the thalamic level, of information passing through the two circuits.     

Afferent thalamic projections in the dog brain pallidal structures

Distribution of labelled neurons in thalamic nuclei after the marker injection into the dog brain pallidal structures (globus pallidum, entopeduncular nucleus and ventral pallidum) was studied by retrograde axonic HRP and fluorochrome transport. Analysis of the material obtained allowed to conclude that in globus pallidum projections from motor thalamic nuclei (ventral anterior, ventral lateral, ventral medial and median centre) are dominating, although in ventral pallidum projections from limbic nuclei (parafascicular and median) are predominant. Entopeduncular nucleus receives projections from functionally different thalamic nuclei (intralaminar and nuclei of ventral and posterior groups). It is obvious that both segregated transmission of functionally specific information and possibility of its convergence at the level of pallidum might occur in organization of thalamo-palidal projections.     

The topographic order of inputs to nucleus accumbens in the rat

Afferents to the nucleus accumbens have been studied with the retrograde transport of unconjugated wheatgerm agglutinin as detected by immunohistochemistry using the peroxidase-antiperoxidase method, in order to define precisely afferent topography from the cortex, thalamus, midbrain and amygdala. Cortical afferent topography was extremely precise. The largest number of cells was found following injections to the anterior accumbens. Anteromedial injections labelled a very large extent of the subiculum and part of the entorhinal cortex. Anterolateral injections produced less subicular and entorhinal label but also labelled the posterior perirhinal cortex. Posteromedial injections labelled only the ventral subiculum and a few cells in the adjacent medial entorhinal cortex. Posterolateral injections labelled few lateral entorhinal neurones but did label a long anteroposterior strip of perirhinal cortex. Prefrontal cortex label was found only after anterior accumbens injections. In the amygdala labelled neurones were found in cortical, central, lateral posterior, anteromedial and basolateral nuclei. Basolateral amygdala projected chiefly to the anteromedial accumbens and central nucleus to anterolateral accumbens. Only a weak amygdala label was found after posterior accumbens injections. In the ventral tegmental area, the midline interfascicular nucleus projected only to medial accumbens. The paranigral ventral tegmentum projected chiefly to the medial accumbens and the parabrachial area chiefly to the lateral accumbens. In the thalamus, heaviest label was found after anterior accumbens injections. Most cells were found in the paraventricular, reuniens and rhomboid nuclei and at posterior thalamic levels lying medial to the fasciculus retroflexus. There was only restricted topography found from thalamic sites. Retrograde label was also found in the ventral pallidum and lateral hypothalamus. Single small injection sites within accumbens received input from the whole anteroposterior extent of the thalamus and ventral tegmentum. The medial accumbens was found to have a close relationship to habenula, globus pallidus and interfascicular nucleus. It appeared that the heaviest volume of inputs projected to anteromedial accumbens, where output from hippocampus (CAI), subiculum, entorhinal and prefrontal cortices converged with output from amygdala, midline thalamus and ventral tegmentum.     

Branched projections in the auditory thalamocortical and corticocortical systems

Branched axons (BAs) projecting to different areas of the brain can create multiple feature-specific maps or synchronize processing in remote targets. We examined the organization of BAs in the cat auditory forebrain using two sensitive retrograde tracers. In one set of experiments (n=4), the tracers were injected into different frequency-matched loci in the primary auditory area (AI) and the anterior auditory field (AAF). In the other set (n=4), we injected primary, non-primary, or limbic cortical areas. After mapped injections, percentages of double-labeled cells (PDLs) in the medial geniculate body (MGB) ranged from 1.4% (ventral division) to 2.8% (rostral pole). In both ipsilateral and contralateral areas AI and AAF, the average PDLs were <1%. In the unmapped cases, the MGB PDLs ranged from 0.6% (ventral division) after insular cortex injections to 6.7% (dorsal division) after temporal cortex injections. Cortical PDLs ranged from 0.1% (ipsilateral AI injections) to 3.7% in the second auditory cortical area (AII) (contralateral AII injections). PDLs within the smaller (minority) projection population were significantly higher than those in the overall population. About 2% of auditory forebrain projection cells have BAs and such cells are organized differently than those in the subcortical auditory system, where BAs can be far more numerous. Forebrain branched projections follow different organizational rules than their unbranched counterparts. Finally, the relatively larger proportion of visual and somatic sensory forebrain BAs suggests modality specific rules for BA organization.     

Chemical organization of projection neurons in the rat accumbens nucleus and olfactory tubercle

Projection neurons in the ventral striatum, the accumbens nucleus and olfactory tubercle, were examined by combining the retrograde tracing method and immunocytochemistry with antibodies against C-terminals of the preprodynorphin (PPD), preproenkephalin (PPE), preprotachykinin A (PPTA) and preprotachykinin B (PPTB). When the retrograde tracer was injected into the ventral pallidum, about 60% and 40% of retrogradely labeled neurons in the accumbens nucleus were immunoreactive for PPD and PPE, respectively. In contrast, all accumbens nucleus neurons projecting to the ventral mesencephalic regions including the substantia nigra and ventral tegmental area were immunopositive for PPD but not for PPE. Although no olfactory tubercle neurons projected fibers to the mesencephalic regions, 60% and 40% of olfactory tubercle neurons projecting to the ventrolateral portion of the ventral pallidum were immunoreactive for PPD and PPE, respectively, as were the accumbens nucleus neurons. About 70% of accumbens nucleus and olfactory tubercle neurons projecting to the ventral pallidum and all accumbens nucleus neurons projecting to the ventral mesencephalic regions showed PPTA immunoreactivity. A small population (2-12%) of accumbens neurons projecting to the ventral pallidum and mesencephalic regions displayed immunoreactivity for PPTB. Compared with the dorsal striatopallidal projection neurons that were reported to mostly express PPE, it was characteristic of the ventral striatum that only the smaller population (about 40%) of ventral striatopallidal projection neurons expressed PPE. This suggests that the ventral striatopallidal projection system is less specialized than the dorsal striatopallidal system in terms of peptide production, or that the ventral pallidum should be compared with a combined region of the globus pallidus and entopeduncular nucleus in the dorsal system.