Modulation of AMPA receptor subunits GluR1 and GluR2/3 in the rat cerebellum in an experimental hepatic encephalopathy model

The immunohistochemical expression and distribution of the AMPA-selective receptor subunits GluR1 and GluR2/3 were investigated in the rat cerebellum following portocaval anastomosis (PCA) at 1 and 6 months. With respect to controls, GluR1 and GluR2/3 immunoreactivities increased over 1 to 6 months following PCA, although immunolabelling patterns for both antibodies were different at the two analysed times. GluR1 immunoreactivity was expressed by Bergmann glial cells, which showed immunoreactive glial processes crossing the molecular layer at 6 months following PCA. The GluR2/3 subunit was expressed by Purkinje neurons and moderately expressed by neurons of the granule cell layer. Immunoreactivity for GluR2/3 was detectable in cell bodies and dendrites of Purkinje cells in young control cerebella, whereas GluR2/3 immunoreactivity was scarce 1 month post PCA. However, despite a lack of immunoreactivity in the Purkinje somata and main processes of adult control rats, GluR2/3 immunoreactivity was strongly enhanced in Purkinje neurons following long-term PCA. These findings suggest that the localization of the GluR2/3 subunit in Purkinje cells undergoes an alteration and/or reorganization as a consequence of long-term PCA. The combination of enhanced GluR immunoreactivity in long-term PCA, both in Bergmann glial cells and in Purkinje neurons, suggests some degree of neuro-glial interaction, possibly through glutamate receptors, in this type of encephalopathy.     

Distribution of AMPA receptor subunits in the nucleus basalis of Meynert in aged humans: implications for selective neuronal degeneration

Immunocytochemical techniques using polyclonal antibodies directed against GluR1 and GluR2/3 subunits of the AMPA-selective receptor complex were used to examine the distribution of these receptor subunits within the nucleus basalis of Meynert (NBM) of non-demented elderly humans. Both somata and processes of magnocellular neurons within the NBM were intensely immunoreactive to GluR1 antibodies. In contrast, within the same region GluR2/3 immunolabeling was largely absent, although GluR2/3-positive neurons were abundantly distributed within adjacent brain regions (i.e., amygdala, entorhinal cortex and hippocampus). These data suggest that NBM neurons may be unique, compared to those of other brain regions, in their response to glutamatergic excitation as mediated via non-NMDA receptors and be particularly vulnerable to glutamate excitotoxicity via a mechanism involving the destabilization of intracellular calcium.     

Regional gene expression of the glutamate receptor subtypes GluR1, GluR2, and GluR3 in human postmortem brain

Although glutamatergic receptors are localized throughout the mammalian central nervous system (CNS), the specific cellular localization of the various glutamatergic receptor subtypes throughout human brain remains largely unknown. PCR fragments to human GluR1, GluR2, and GluR3 receptor subtypes were cloned and used as probes forin situ hybridization in order to examine the anatomical and cellular localization of glutamate receptor subtype gene expression in dissected regions of human postmortem brain tissue. Although hybridization was observed throughout the CNS, results indicated that the highest levels of hybridization were in the hippocampus, with localization primarily to cells in the pyramidal cell layer of the CA1-CA3 region, and the granular cells of the dentate gyrus. Prominent hybridization also was observed in the medium to large neurons of the cingulate cortex, temporal lobe, septum, and amygdala, as well as in scattered neurons in the thalamus, cerebral cortex, and medulla. A striking pattern of differential hybridization was observed within the cerebellum. GluR1 demonstrated light hybridization along the Purkinje/Bergmann glia layer, with GluR2 and GluR3 demonstrating hybridization to Purkinje cells, and GluR3 also to cells within the molecular layer, previously identified as stellate-basket cells. Changes in glutamate receptor function have been shown to be important in the pathogenesis of a number of neurological disorders. Therefore, an examination of glutamatergic receptor expression in human postmortem brain tissue may provide important information on the molecular basis of a variety of neurological and psychiatric disorders of the CNS.     

The Distribution of Neurons Coexpressing Immunoreactivity to AMPA-sensitive Glutamate Receptor Subtypes (GluR1-4) and Nerve Growth Factor Receptor in the Rat Basal Forebrain

The regional distribution of neurons containing a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor (GluR1-4) subunit immunoreactivity, relative to the distribution of cholinergic neurons within the basal forebrain of rats, was assessed using single- and dual-antigen immunocytochemistry. Analysis of serial sections stained with antibodies to nerve growth factor receptor (NGFr) and antibodies against each of the AMPA receptor subunits, GluR1-4, revealed a regional codistribution between NGFr- and GluR1- and GluR4-immunoreactive neurons in the medial septum, diagonal band nuclei and nucleus basalis magnocellularis. Quantitative dual-labelling immunocytochemistry using NGFr in combination with each of the GluR antibodies revealed >65% colocalization between NGFr and GluR4 in each of the major cholinergic nuclei in the basal forebrain and 10–15% colocalization between NGFr, GluR1 and GluR2-3. The reticular nucleus of the thalamus, a structure known to be highly susceptible to AMPA-induced neurotoxicity, expressed GluR4 immunoreactivity exclusively. The observation that cholinergic neurons of the basal forebrain are also highly sensitive to AMPA and express the GluR4 subunit suggests that GluR4 may be important in AMPA receptor-mediated excitotoxicity.     

Age-related vulnerability to nigral dopaminergic degeneration in rats via Zn2+-permeable GluR2-lacking AMPA receptor activation

On the basis of the evidence that extracellular Zn²⁺ influx induced with AMPA causes Parkinson's syndrome in rats that apomorphine-induced movement disorder emerges, here we used a low dose of AMPA, which does not increase intracellular Zn²⁺ level in the substantia nigra pars compacta (SNpc) of young adult rats, and tested whether intracellular Zn²⁺ dysregulation induced with AMPA is accelerated in the SNpc of aged rats, resulting in age-related vulnerability to Parkinson's syndrome. When AMPA (1 mM) was injected at the rate of 0.05 μl/min for 20 min into the SNpc, intracellular Zn²⁺ level was increased in the SNpc of aged rats followed by increase in turning behavior in response to apomorphine and nigral dopaminergic degeneration. In contrast, young adult rats do not show movement disorder and nigral dopaminergic degeneration, in addition to no increase in intracellular Zn²⁺. In aged rats, movement disorder and nigral dopaminergic degeneration were rescued by co-injection of either extracellular (CaEDTA) or intracellular (ZnAF-2DA) Zn²⁺ chelators. 1-Naphthyl acetyl spermine (NASPM), a selective blocker of Ca²⁺- and Zn²⁺-permeable GluR2-lacking AMPA receptors blocked increase in intracellular Zn²⁺ in the SNpc of aged rats followed by rescuing nigral dopaminergic degeneration. The present study indicates that intracellular Zn²⁺ dysregulation is accelerated by Ca²⁺- and Zn²⁺-permeable GluR2-lacking AMPA receptor activation in the SNpc of aged rats, resulting in age-related vulnerability to Parkinson's syndrome.     

Cellular localization of GluR1, GluR2/3 and GluR4 glutamate receptor subunits in neurons of the rat neostriatum

Glutamate excitocytotoxicity is implied in the cause of neuronal degeneration in the neostriatum, in which the toxicity may be mediated by different families of glutamate receptors. The precise cellular localization of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA)-type glutamate receptor subunits (GluR1–4), one of the major family that involves in the mechanisms of glutamate excitocytotoxicity, in different populations of striatal neurons is therefore of special interest. Immunoreactivity for GluR2/3 subunits was detected in the medium-sized spiny neurons. By double labelling experiments, immunoreactivity for GluR1 and GluR4 was detected only in aspiny striatal neurons that display parvalbumin immunoreactivity, but not in the other neuron populations that display choline acetyltransferase or muscarinic m2 receptor immunoreactivity, nor neurons that display nitric oxide synthase immunoreactivity or nicotinamide adenine dinucleotide phosphate-diaphorase activity. These results indicate that GluR1 and GluR4 immunoreactivity is displayed only in the GABAergic interneurons in the neostriatum. In addition, almost all of the GluR1-immunoreactive neurons were found to display GluR4 immunoreactivity. This finding indicates for the first time that the striatal GABAergic interneurons co-express GluR1 and GluR4 subunits. The results of the present study indicate that there is a differential localization of AMPA-type glutamate receptor subunits in different populations of striatal neurons and they may have a different susceptibility to glutamate excitocytotoxicity.     

AGS-induced expression of Narp is concomitant with expression of AMPA receptor subunits GluR1 and GluR2 in hippocampus but not inferior colliculus of P77PMC rats

To explore mechanisms of epileptogenesis in audiogenic seizures (AGS), we examined the expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazoleopropionic acid (AMPA) receptor subunits GluR1 and GluR2 and of the GluR-associated protein Narp in the hippocampus and the inferior colliculus (IC) from AGS-susceptible P77PMC rats after a single AGS and audiogenic kindling. Western blotting and immunohistochemistry showed that Narp was rapidly induced in both the hippocampus and the IC by AGS. In the hippocampus, up-regulation of Narp was concomitant with GluR1 and GluR2 under both conditions of a single AGS and AGS kindling. In the IC, however, Narp was up-regulated, GluR2 down-regulated, and GluR1 unchanged after kindling. In comparison with kindling, neither GluR1 nor GluR2 was changed, while Narp significantly increased in the IC following a single AGS. These findings suggest that down-regulation of AMPA receptor GluR2 subunit in the IC may contribute to AGS-mediated epileptogenesis, and up-regulation of Narp in the IC may be involved in audiogenic seizures.     

Neurokinin 1 receptor-expressing projection neurons in laminae III and IV of the rat spinal cord have synaptic AMPA receptors that contain GluR2, GluR3 and GluR4 subunits

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPArs), which mediate fast excitatory glutamatergic transmission, are tetramers made from four subunits (GluR1–4 or GluRA–D). Although synaptic AMPArs are not normally detected by immunocytochemistry in perfusion-fixed tissue, they can be revealed by using antigen retrieval with pepsin. All AMPAr-positive synapses in spinal cord are thought to contain GluR2, while the other subunits have specific laminar distributions. GluR4 can be alternatively spliced such that it has a long or short cytoplasmic tail. We have reported that <10% of AMPAr-containing synapses in lamina II have the long form of GluR4, and that these are often arranged in dorsoventrally orientated clusters. In this study, we test the hypothesis that GluR4-containing receptors are associated with dorsal dendrites of projection neurons in laminae III and IV that express the neurokinin 1 receptor (NK1r). Immunostaining for NK1r was carried out before antigen retrieval, and sections were then reacted to reveal GluR2 and either GluR4 (long form), GluR3 or GluR1. All NK1r-positive lamina III/IV neurons had numerous GluR2-immunoreactive puncta in their dendritic plasma membranes, and virtually all (97%) of the puncta tested were labelled (usually strongly) with the GluR4 antibody. Sizes of puncta varied, but many were elongated and they were significantly larger than nearby puncta that were not associated with the NK1r cells. None of the GluR2 puncta on these cells was positive for GluR1, while 85% were GluR3-immunoreactive. These results show that synaptic AMPArs on the dendrites of the lamina III/IV NK1r projection neurons contain GluR2, GluR3 and GluR4, but not GluR1 subunits.     

Expression of AMPA receptor subunits (GluR1-GluR4) in gonadotrophin-releasing hormone neurones of young and middle-aged persistently oestrous rats during the steroid-induced luteinising hormone surge

Glutamate provides excitatory input to gonadotrophin-releasing hormone (GnRH) neurones and elicits a response indicative of AMPA receptors. To determine if and which AMPA subunits are expressed by GnRH neurones, we conducted triple-label immunohistochemistry and confocal analyses on tissue obtained at 08.00, 12.00, 16.00 and 20.00 h from young and middle-aged, persistently oestrous (MA-PE) rats that were ovariectomised and primed with oestrogen and progesterone to induce a luteinising hormone (LH) surge. Each AMPA subunit was found in GnRH neurones, but in different patterns across the diurnal cycle, which were influenced by age. GluR1 expression increased earlier in young rats and the percentage of Fos-positive GnRH neurones expressing GluR1 rose significantly and was sustained from 12.00-16.00 h. GluR1 expression was delayed in MA-PE rats and the percentage of Fos-positive GnRH neurones expressing GluR1 peaked at 20.00 h. GluR2 expression in GnRH neurones did not change over time and was not affected by age; however, the percentage of Fos-positive GnRH neurones expressing GluR2 increased earlier and was sustained from 08.00-16.00 h in young rats whereas, in MA-PE rats, this percentage peaked at 20.00 h. GluR3 expression also increased earlier in young rats and peaked at 12.00 h but was delayed in MA-PE rats and peaked at 20.00 h. The number of Fos-positive GnRH neurones that coexpressed GluR3 peaked at 12.00 h in young rats but showed little change from 12.00-20.00 h in MA-PE rats. GluR4 expression was maintained at higher levels at 08.00 and 12.00 h in young rats; although the percentage of Fos-positive GnRH neurones expressing GluR4 peaked at 12.00 h in young rats, it showed little change in MA-PE rats. In summary, our data show that a higher proportion of Fos-positive GnRH neurones coexpressed AMPA receptor subunits in young rats and the expression, particularly of GluR1 and GluR2, was increased and sustained throughout the surge, whereas GluR3 and GluR4 expression peaked just before. In MA-PE rats, the rate of expression of GluR subunits and Fos in GnRH neurones was altered in a manner that may explain the delay and attenuation of the LH surge.     

Activity regulates the expression of AMPA receptor subunit GluR4 in developing visual cortex

In the developing visual cortex, the expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit GluR4 precedes that of the other AMPAR subunits GluR1-3, and then declines to become almost absent in adults. The current study shows that the neuronal activity regulates the expression of GluR4 by a culture system in vitro and a dark-rearing (DR) system in vivo. Membrane depolarization by treatment of cultured neurons of the visual cortex with a high concentration of KCl (35 mm; HK) promoted a decline in the expression of GluR4. This effect of HK on the expression of GluR4 was significantly blocked by the addition of an N-methyl-d-aspartate receptor (NMDAR) antagonist, (D)-2-amino-5-phosphonovaleric acid (APV), but not by the voltage-sensitive calcium channel antagonist nifedipine. Moreover, the Ca(2+)-calmodulin-dependent kinase (CaMKII) inhibitor KN62 and the cAMP-dependent protein kinase A (PKA) inhibitor H-89 blocked this effect, which suggests the involvement of Ca(2+) influx via NMDAR and the subsequent activation of CaMKII and PKA. Conversely, the MAP kinase inhibitor PD98059 promoted the effect of HK on the expression of GluR4. Significantly, APV, KN62, H-89 and PD98059 either promoted or inhibited the expression of GluR4 even in normal KCl (5 mm) conditions. The developmental change in the expression of GluR4 was significantly attenuated in DR in vivo, and the results suggest that neuronal activity such as visual experience may be involved in the mechanism of the expression of GluR4, which is mediated by NMDAR and tuned by certain protein kinases at an early developmental stage in the visual cortex.     

Distribution of glutamate receptor subunits at neurochemically characterized synapses in the entopeduncular nucleus and subthalamic nucleus of the rat

Glutamatergic neurotransmission in the subthalamic nucleus (STN) and in the output nuclei of the basal ganglia is critical in the expression of basal ganglia function, and increased glutamate transmission in these nuclei has been implicated in the pathology of Parkinson's disease. In order to determine the precise spatial relationship of subunits of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and N-methyl-D-aspartate (NMDA) glutamate receptors to nerve terminals enriched in glutamate or γ-aminobutyric acid (GABA) in one of the output nuclei, the entopeduncular nucleus (EP), and the STN, postembedding immunolabelling for glutamate receptor subunits and for glutamate and GABA was carried out in the rat. Immunolabelling for the AMPA glutamate receptor subunits 1, 2/3, and 4 (GluR1, GluR2/3, and GluR4) and the NMDA receptor subunit 1 (NR1) was localized predominantly within asymmetrical synapses in both the EP and STN. Quantitative analysis revealed that, on average for the whole population, each of the receptor subunits was evenly distributed along the synaptic specialization. Multiple AMPA receptor subunits and the GluR2/3 and NMDA (NR1) subunits were co-localized within individual synapses. The combination of immunolabelling for glutamate and GABA with the receptor immunolabelling revealed that the majority of axon terminals presynaptic to the receptor-immunoreactive synapses were enriched in glutamate immunoreactivity and were GABA-immunonegative. However, at some NR1- and GluR2/3-positive synapses, the level of glutamate immunoreactivity was low in the presynaptic terminal and, in the STN, some of them were GABA-immunopositive. It is concluded that glutamatergic transmission at individual synapses of different origins in the EP and STN is mediated by a combination of AMPA and NMDA glutamate receptors. J. Comp. Neurol. 397:403–420, 1998. © 1998 Wiley-Liss, Inc.     

The organization of AMPA receptor subunits at the postsynaptic membrane

AMPA receptors are the principal mediators of excitatory synaptic transmission in the mammalian central nervous system. The subunit composition of these tetrameric receptors helps to define their functional properties, and may also influence the synaptic trafficking implicated in long‐term synaptic plasticity. However, the organization of AMPAR subunits within the synapse remains unclear. Here, we use postembedding immunogold electron microscopy to study the synaptic organization of AMPAR subunits in stratum radiatum of CA1 hippocampus in the adult rat. We find that GluA1 concentrates away from the center of the synapse, extending at least 25 nm beyond the synaptic specialization; in contrast, GluA3 is uniformly distributed along the synapse, and seldom extends beyond its lateral border. The fraction of extrasynaptic GluA1 is markedly higher in small than in large synapses; no such effect is seen for GluA3. These observations imply that different kinds of AMPARs are differently trafficked to and/or anchored at the synapse. © 2014 Wiley Periodicals, Inc.     

Subunit selective decrease of AMPA and metabotropic glutamate receptor mRNA expression in rat brain by systemic administration of the NMDA receptor blocker MK-801

Glutamate mediates its effects in mammals through both ionotropic and metabotropic receptors. Antagonists of ionotropic N-methyl-d-aspartate (NMDA) glutamate receptors elicit neuroprotective and neurotropic effects that have been attributed to Ca²⁺ block through the membrane ion channel. Nonetheless, molecular and biochemical effects of NMDA receptor antagonism on other glutamate receptor subunits remain poorly understood. We investigated the effects of acute administration of the noncompetitive NMDA receptor antagonist MK-801 on the mRNA expression of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and metabotropic glutamate receptor (mGluR) subunits to determine the contribution of different glutamate receptors in response to blockade of NMDA receptor channels. In situ hybridization to rat brain sections revealed that AMPA receptor subunits GluR3 and GluR4, and mGluR3 were modestly but significantly decreased ∼10–20%, 8 h following 5 mg/kg MK-801 administration. A time course and dose response study revealed that the effect on mGluR3 was reversed by 24 h and occurred significantly at a dose range from 1 to 5 mg/kg. These results indicate that selected AMPA and mGluR subunit mRNAs respond at the RNA level to the blockade of NMDA receptors.     

Nucleus basalis of Meynert neuronal activity during a delayed response task in monkey

A total of 183 nucleus basalis of Meynert (NBM) neurons were recorded in a monkey performing a delayed response task. Significant changes in discharge rate were detected in 74% of the NBM cells sampled with most responses occurring in the choice (64%) or the reward (67%) epochs of the task. Neuronal responses in the cueing epoch were less common (31%) and less robust than in the choice epoch, although the animal made essentially the same arm movement in both cases. Only 14% of the task-related NBM cells had significant changes in discharge rate in the delay period, and none of these responded differentially for the two positions indicated in the preceding cueing epoch. These findings do not support a role of the NBM in the differential responses of cortical neurons in delayed response tasks, but they provide further evidence for NBM involvement in aspects of reward acquisition.     

AMPA-Selective glutamate receptor subunits in astroglial cultures

We analysed AMPA ionotropic receptor subunits at the mRNA level (GluR-1 to -4) and at the protein level (GluR-1 and GluR-2/3/4C) in “primary astroglial cultures” (non-neuronal cell cultures highly enriched in glial fibrillary acidic protein [GFAP] positive cells) prepared from newborn rat cerebral hemispheres, cerebral cortex, hippocamps, and striatum and in “brain non-neuronal cell cultures” (low percentage of GFAP positive cells) prepared from cerebellum, brainstem, mesencephalon, and hypothalamus. For comparison, we also determined ampa subunit mRNA and protein levels in different brain regions. By Northern blot analysis mRNAs for the AMPA receptor subunits (glur-1,-2,-3,-4) were detected in primary rat cerebral hemispheres astroglial cultures. Immunoblotting analysis with anti-GluR-1 and anti GluR-2/3/4C polyclonal antibodies confirmed the presence of low leve of immunoreactive proteins of the same size of those identifice in vivo as GluR subunits. Expression of GluR genes varied depending on the brain area used as starting material for the preparation of the cultures: GluR-1, -2, and -3 were mailly expressed in cortical cultures, while GluR-4 expression predominated in brainstem derived cultures. Interestingly this pattern of expression correlates with that observed in the intact brain, where high levels of GluR-4 mRNA and low levels of the other GluR subunits were found in the brainstem. In conclusion our results confirm the existence of glutmate ionotropic receptors of the AMPA type in primary astroglial cultrues and suggest that GluR-4 is the main AMPA receptor subunit expressed in non neuronal cells of the central nervous system. © 1993 Wiley-Liss, Inc.     

Subcellular and subsynaptic distribution of the NR1 subunit of the NMDA receptor in the neostriatum and globus pallidus of the rat: co-localization at synapses with the GluR2/3 subunit of the AMPA receptor

Glutamatergic neurotransmission in the neostriatum and the globus pallidus is mediated through NMDA-type as well as other glutamate receptors and is critical in the expression of basal ganglia function. In order to characterize the cellular, subcellular and subsynaptic localization of NMDA receptors in the neostriatum and globus pallidus, multiple immunocytochemical techniques were applied using antibodies that recognize the NR1 subunit of the NMDA receptor. In order to determine the spatial relationship between NMDA receptors and AMPA receptors, double labelling was performed with the NR1 antibodies and an antibody that recognizes the GluR2 and 3 subunits of the AMPA receptor. In the neostriatum all neurons with characteristics of spiny projection neurons, some interneurons and many dendrites and spines were immunoreactive for NR1. In the globus pallidus most perikarya and many dendritic processes were immunopositive. Immunogold methods revealed that most NR1 labelling is associated with asymmetrical synapses and, like the labelling for GluR2/3, is evenly spread across the synapse. Double immunolabelling revealed that in neostriatum, over 80% of NR1-positive axospinous synapses are also positive for GluR2/3. In the globus pallidus most NR1-positive synapses are positive for GluR2/3. In both regions many synapses labelled only for GluR2/3 were also detected. These results, together with previous data, suggest that NMDA and AMPA receptor subunits are expressed by the same neurons in the neostriatum and globus pallidus and that NMDA and AMPA receptors are, at least in part, colocalized at individual asymmetrical synapses. The synaptic responses to glutamate in these regions are thus likely be mediated by both AMPA and NMDA receptors at the level of individual synapses.     

Dopamine D5 receptor localization on cholinergic neurons of the rat forebrain and diencephalon: a potential neuroanatomical substrate involved in mediating dopaminergic influences on acetylcholine release

The study of dopaminergic influences on acetylcholine release is especially useful for the understanding of a wide range of brain functions and neurological disorders, including schizophrenia, Parkinson's disease, Alzheimer's disease, and drug addiction. These disorders are characterized by a neurochemical imbalance of a variety of neurotransmitter systems, including the dopamine and acetylcholine systems. Dopamine modulates acetylcholine levels in the brain by binding to dopamine receptors located directly on cholinergic cells. The dopamine D5 receptor, a D1-class receptor subtype, potentiates acetylcholine release and has been investigated as a possible substrate underlying a variety of brain functions and clinical disorders. This receptor subtype, therefore, may prove to be a putative target for pharmacotherapeutic strategies and cognitive-behavioral treatments aimed at treating a variety of neurological disorders. The present study investigated whether cholinergic cells in the dopamine targeted areas of the cerebral cortex, striatum, basal forebrain, and diencephalon express the dopamine D5 receptor. These receptors were localized on cholinergic neurons with dual labeling immunoperoxidase or immunofluorescence procedures using antibodies directed against choline acetyltransferase (ChAT) and the dopamine D5 receptor. Results from this study support previous findings indicating that striatal cholinergic interneurons express the dopamine D5 receptor. In addition, cholinergic neurons in other critical brain areas also show dopamine D5 receptor expression. Dopamine D5 receptors were localized on the somata, dendrites, and axons of cholinergic cells in each of the brain areas examined. These findings support the functional importance of the dopamine D5 receptor in the modulation of acetylcholine release throughout the brain.     

Distribution of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate-type glutamate receptor subunits (GluR2/3) along the ventral visual pathway in the monkey

By using immunohistochemical methods, we examined the distribution of cells expressing subunits of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-selective glutamate receptors (GluR2/3) in the cortical areas of the occipitotemporal pathway in monkeys. GluR2/3-immunoreactive (-ir) cells were primarily pyramidal cells; this category, however, also included large stellate cells in layer IVB of the striate cortex (V1) and fusiform cells in layer VI of all the areas examined. GluR2/3 immunoreactivity differed among the areas in laminar distribution and intensity. In V1, GluR2/3-ir cells were identified mainly in layers II, III, IVB, and VI. The prestriate areas V2 and V4 and the inferior temporal areas TEO and TE contained GluR2/3-ir cells in layers II, III, and VI. In the TE, GluR2/3-ir cells were also abundant in layer V. In area 36 of the perirhinal cortex, neurons in layers II, III, V, and VI were labeled in a similar manner to the TE labeling, but with greater staining intensity and numbers, especially in layer V. Thus, GluR2/3 immunoreactivity increased rostrally along the pathway. Within V1 and V2, cells strongly stained for GluR2/3 formed clusters that colocalized with cytochrome oxidase (CO)-rich regions. These distinct laminar and regional distribution patterns of GluR2/3 expression may contribute to the specific physiological properties of neurons within various visual areas and compartments.