5-HT2A receptor antagonist M100907 reduces serotonin synthesis: an autoradiographic study

The effects of the administration of the serotonin (5-HT)_2A antagonist, M100907, on 5-HT synthesis rates, were evaluated using the α-[¹⁴C]methyl-l-tryptophan (α-MTrp) autoradiographic method. In the treatment study, M100907 (10 mg/kg) was injected intraperitoneally 30 min before the α-MTrp injection (30 μCi over 2 min). A single dose of M100907 caused a significant decrease in the synthesis in the anterior olfactory nucleus, accumbens nucleus, frontal cortex, sensory-motor cortex, cingulate cortex, medial caudate-putamen, dorsal thalamus, substantia nigra, inferior collicus, raphe magnus nucleus, superior olive, and raphe pallidus nucleus.These data suggest that the terminal 5-HT_2A receptors are involved in the regulation of 5-HT synthesis in the entire brain. Further, 5-HT synthesis is likely regulated by the 5-HT_2A antagonistic property of M100907 in the cortices, anterior olfactory nucleus, caudate putamen, and nucleus accumbens.     

Age-dependent changes in adenosine A1 receptor and uptake site binding in the mouse brain: an autoradiographic study

Ageing is a multifactorial, inevitable event of life span, which affects neurotransmission in the CNS. Since adenosine is a major neuromodulator of the synaptic activity, it was of interest to investigate the possible modification of the adenosinergic system in the brain during ageing. Using "in vitro" quantitative autoradiography and the radioactive ligands [(3)H]Cyclohexyladenosine and [(3)H]Nitrobenzylthioinosine, we have studied the distribution of A1 adenosine receptors and adenosine uptake sites in the aged mice (26 months) compared to the young ones (3 months). Our results showed a widespread reduction in A1 receptor binding in the aged animals, which was brain area-specific, occurring in areas where adenosine plays a significant neuromodulatory role such as the hippocampus, cortex, basal ganglia, and thalamus. Interestingly, the significant reduction in NBI-sensitive adenosine uptake sites was restricted to few areas of the aged brain, mainly in thalamic nuclei. Since the alterations in the density of A1 receptors and adenosine uptake sites showed no regional correlation and since no significant changes in either neuronal or glial cell number are observed, at least in hippocampus and cortex in this mouse strain during ageing, our findings could be explained by a selective age-dependent reduction of these adenosinergic components rather than by a general neuronal cell degeneration. As adenosine depresses electrical activity in hippocampus, a downregulation of adenosinergic function could probably be related to enhanced excitability seen in hippocampal neurons of the CA1 subregion and dentate gyrus of aged animals.     

Further postmortem autoradiographic studies of AMPA receptor binding in schizophrenia

Previous research indicated an increased binding of AMPA receptor ligand [(3)H]CNQX at 50 nM in the caudate nucleus of schizophrenics and suicides relative to normal and neuroleptic-treated controls. The current work aimed to replicate this finding in a larger, independent sample of schizophrenics and controls. In addition to neostriatal structures, the hippocampal region and amygdala were also studied. Postmortem frozen sections from 15 schizophrenics (four suicides), 15 normal controls, 15 bipolars (eight suicides), and 15 unipolar nonpsychotic depressed (seven suicides) subjects were studied with quantitative autoradiographic procedures at 5, 20, and 50 nM [(3)H]CNQX in the striatum and at 20 nM in medial temporal structures. [(3)H]KA (kainic acid) binding was also examined. Instead of an expected increase, schizophrenics in this sample have a lower degree of [(3)H]CNQX binding in caudate and nucleus accumbens at 20 nM and in the nucleus accumbens at 50 nM, with suicided schizophrenics having higher binding than nonsuicided schizophrenics at the 20 nM concentration of [(3)H]CNQX in the caudate. [(3)H]CNQX binding was uniform across diagnostic categories at 5 nM in the striatum and at 20 nM in amygdala and hippocampal structures. KA receptor binding also did not differ among groups in any structures examined. These assays in a larger sample at three different concentrations do not support the previously reported increase in binding to AMPA receptors in schizophrenia but rather indicate an abnormal decrease in binding to this receptor in this sample. Possible explanations for the disparity in results between the two studies are considered. The data continue to indicate pathology of AMPA glutamate receptors in striatal structures in schizophrenia; however, it may be variable and its precise nature remains to be clarified.     

Interferon-γ-induced changes in synaptic activity and AMPA receptor clustering in hippocampal cultures

Extended release of interferon-γ (IFN-γ) in the nervous system during immunological and infectious conditions may trigger demyelinating disorders and cause disturbances in brain function. The aim of this study was to examine the effects of IFN-γ on neuronal function in rat hippocampal cell cultures by using whole cell patch clamp analysis together with quantitative immunocytochemistry. Acute application of IFN-γ to differentiated neurons in culture caused no immediate neurophysiological responses, but recordings after 48 h of incubation displayed an increase in frequency of AMPA receptor (AMPAR)-mediated spontaneous excitatory postsynaptic currents (EPSCs). Quantitative immunocytochemistry for the AMPAR subunit GluR1 showed no alteration in receptor clustering at this time point. However, prolonged treatment with IFN-γ for 2 weeks resulted in a significant reduction in AMPAR clustering on dendrites but no marked differences in EPSC frequency between treated neurons and controls could be observed. On the other hand, treatment of hippocampal neurons for 4 weeks, instituted at an immature stage (1 day in culture), caused a significant reduction in spontaneous EPSC frequency. These neurons developed with no overt alterations in dendritic arborization or in the appearance of dendritic spines as visualized by α-actinin immunocytochemistry. Nonetheless, there was a marked reduction in AMPAR clustering on dendrites. These observations show that a key immunomodulatory molecule, IFN-γ, can cause long-term modifications of synaptic activity and perturb glutamate receptor clustering.     

Chronic theophylline treatment increases adenosine A1, but not A2, receptor binding in the rat brain: an autoradiographic study.

Chronic exposure to adenosine receptor antagonists results in an upregulation of brain adenosine A1 receptors as measured by traditional radioligand binding techniques. In the present study, quantitative receptor autoradiography was used to characterize alterations in rat brain adenosine A1 and A2 receptors following the repeated administration of high doses of theophylline. Daily administration of theophylline (75 or 100 mg/kg) markedly increased (125-150% of control) 1 nM [3H]cyclohexyladenosine binding to adenosine A1 receptors in specific cellular layers of the hippocampus, thalamus, and cerebellum with other brain regions showing more moderate increases in binding. By contrast, this chronic theophylline treatment did not produce any significant alterations in the binding of 4 nM [3H]CGS 21680 to adenosine A2 receptors, which were exclusively localized in the striatal region. This apparent differential sensitivity of adenosine receptor subtypes to chronic antagonist treatment suggests a possible intrinsic difference in the regulation of these receptor subtypes which may also be specific to particular brain regions. These results are discussed in relationship to other recent observations, indicating that the pattern of agonist binding to adenosine receptors may be regulated by a differential extent of coupling between adenosine receptors and G-binding proteins in different brain regions.     

Ageing-related decline in adenosine A1 receptor binding in the rat brain: an autoradiographic study

The adenosine system has important neuromodulatory and neuroprotective functions in the brain. Several lines of evidence suggest that ageing is associated with major alterations in the adenosine system, which may be partially responsible for changes in sleep, mood, and cognition. In the present study, we examined adenosine A1 receptor density in the rat brain by means of quantitative autoradiography to obtain a detailed anatomical overview of the changes during ageing. A1 receptor binding was assessed in young, old, and senescent animals of 3, 24, and 30 months old, respectively. There was a clear age-dependent reduction in adenosine A1 receptors in most of the brain areas examined, but the magnitude of this reduction varied greatly among regions. Also, whereas some regions displayed a gradual decline in A1 binding sites across the three age classes, other regions showed a particularly strong decrease between the ages of 24 and 30 months. For example, whereas the hippocampus and thalamus showed a gradual decline in A1 binding, some cortical and septal regions showed a more abrupt decline after the age of 24 months. Since particularly in rats many studies have used animals at the age of 24 months or even less, the ageing-related decline in adenosine A1 signaling might have been underestimated.     

An autoradiographic study of [H]AMPA receptor binding and in situ hybridization of AMPA sensitive glutamate receptor A (GluR-A) subunits following morphine withdrawal in the rat brain

Chronic treatment with opioids is well known to result in the development of physical dependence. More recently, glutamatergic mechanisms have been implicated in expression of the withdrawal syndrome from opioids. To better examine glutamatergic involvement, an autoradiographic study of [³H]AMPA receptor binding and an assessment of in situ hybridization of AMPA sensitive glutamate receptor A (GluR-A) subunits in the rat brain were each performed 7 h after withdrawal from morphine infusion. Animals were rendered dependent by intracerebroventricular (i.c.v.) infusion of morphine (26 nmol/μl/h) via osmotic minipumps for 3 days. Brain sections of 14-μm thickness were incubated with 15 nM [³H]AMPA for quantitation of binding to the AMPA receptor. The probe for in situ hybridization was labeled at its 3′ end using terminal deoxynucleotidyl transferase and [³⁵S]dATP. The highest degree of [³H]AMPA binding was shown in the hippocampus. The extent of [³H]AMPA binding was increased significantly in the cortex areas (18–21%), caudate-putamen (20%), and hippocampus (7–9%) of rats following withdrawal from morphine. The highest levels of mRNA for GluR-A, flop and flip subunits, were found in the dentate gyrus and in the CA3 region of the hippocampus, respectively. The levels of mRNA for the flop form of GluR-A were decreased in the CA3 of hippocampus (8%) of the rat brain. The levels of mRNA for the flip form of GluR-A were increased in the parietal cortex (7%) and the entorhinal cortex (8%). Increases in the binding of [³H]AMPA to its receptor may play an important role during withdrawal from morphine dependence.     

An autoradiographic study of [3H]AMPA receptor binding and in situ hybridization of AMPA sensitive glutamate receptor A (GluR-A) subunits following morphine withdrawal in the rat brain

Chronic treatment with opioids is well known to result in the development of physical dependence. More recently, glutamatergic mechanisms have been implicated in expression of the withdrawal syndrome from opioids. To better examine glutamatergic involvement, an autoradiographic study of [3H]AMPA receptor binding and an assessment of in situ hybridization of AMPA sensitive glutamate receptor A (GluR-A) subunits in the rat brain were each performed 7 h after withdrawal from morphine infusion. Animals were rendered dependent by intracerebroventricular (i.c.v.) infusion of morphine (26 nmol/microl/h) via osmotic minipumps for 3 days. Brain sections of 14-microm thickness were incubated with 15 nM [3H]AMPA for quantitation of binding to the AMPA receptor. The probe for in situ hybridization was labeled at its 3' end using terminal deoxynucleotidyl transferase and [35S]dATP. The highest degree of [3H]AMPA binding was shown in the hippocampus. The extent of [3H]AMPA binding was increased significantly in the cortex areas (18-21%), caudate-putamen (20%), and hippocampus (7-9%) of rats following withdrawal from morphine. The highest levels of mRNA for GluR-A, flop and flip subunits, were found in the dentate gyrus and in the CA3 region of the hippocampus, respectively. The levels of mRNA for the flop form of GluR-A were decreased in the CA3 of hippocampus (8%) of the rat brain. The levels of mRNA for the flip form of GluR-A were increased in the parietal cortex (7%) and the entorhinal cortex (8%). Increases in the binding of [3H]AMPA to its receptor may play an important role during withdrawal from morphine dependence.     

Nigrotectal projections in the monkey: an autoradiographic study.

The changed patterns of proteolytic activity in brain and spinal cord of Lewis rats were examined in 4 different morphological variants of EAE: ordinary induced by the standard emulsion, hyperacute induced by an emulsion plus pertussis vaccine, passive induced by donor EAE cells, and monocytic induced by treatment of passive EAE with the immunosuppressive drug tilorone. The following enzymatic changes were found: firstly, in ordinary EAE there was a 2–3.5-fold increase in cathepsins A and C (E.C. 3.4.14.1) in spinal cord one day following the appearance of paralysis with a smaller change in hindbrain, and none in the forebrain regions. With recovery from paralysis, levels of cathepsin A remained high in upper cord, and cathepsin C levels fell to about half. In contrast, increase in cathepsin D (E.C.3.4.23.5) was smaller and occurred only 4–5 days after paralysis with the largest change in spinal cord areas and with only a small decrease on recovery from paralysis.Secondly, in hyperacute EAE, the increase in all cases was smaller with the largest change in cathepsin A level in upper spinal cord. In passive EAE, the most significant increase occurred only in the lower spinal cord for cathepsins A and C, and fourthly, in monocytic EAE induced by tilorone, there was an exceptionally large, 3-fold increase in cathepsin C in lower cord as compared to a 1.5–2 fold increase for other cathepsins.No major differences were observed on comparison of antigens from different sources (guinea pig and bovine spinal cord myelin peptide). An attempt is made to relate enzymatic changes to the morphological features of each variant with special reference to the nature of the infiltrating cells.     

Ontogenetic changes in vasopressin binding site distribution in rat brain: an autoradiographic study

Binding sites for [3H]vasopressin were identified in brains of neonatal (days 0-23) and adult (90 day) Long-Evans and Brattleboro rats, using a technique of in vitro receptor autoradiography. Results indicate that the regional distribution of binding sites for [3H]vasopressin in the brain changes markedly during postnatal development. Binding sites in the septum proliferated slowly to attain adult distribution in the dorsal and lateral septum, while in other regions, such as the caudate, hippocampus and cingulate gyrus, intense labeling appeared early in development but disappeared by adulthood. In the amygdala, binding did not change during postnatal development. Binding sites in the septum appeared before vasopressinergic fibers are present. Also, binding was present for vasopressin in regions which have not yet been reported to receive vasopressinergic innervation. Therefore, it is proposed that the presence of binding sites for vasopressin is independent of the presence of vasopressin itself. This hypothesis is supported by labeling in the Brattleboro rat which was comparable to that in the Long-Evans.     

Fastigial efferent projections in the monkey: an autoradiographic study.

Because fastigial efferent fibers partially decussate within the cerebellum and cerebellar corticovestibular projections pass near, or through, the fastigial nucleus (FN), degeneration studies based on lesions in the nucleus leave unresolved questions concerning fastigial projections. Attempts were made to determine fastigial projections in the monkey using autoradiographic tracing technics. Cells in rostral, caudal and all parts of the FN were labeled with [³H] amino acids. Selective labeling of neurons in either rostral or caudal parts of the FN results in transport of isotope primarily via fibers of the contralateral uncinate fasciculus (UF) and the ipsilateral juxtarestiform body (JRB). Fastigial projections to the vestibular nuclei are mainly to ventral portions of the lateral (LVN) and inferior (IVN) vestibular nuclei, are nearly symmetrical and are quantitatively similar on each side. Fastigiovestibular projections to cell groups f and x arise from all parts of the FN and are mainly crossed; modest projections to the medial vestibular nucleus are uncrossed. No fastigial efferent fibers end in the superior vestibular nucleus on either side, or in dorsal regions of the LVN. Crossed fibers descending in IVN terminate in the nucleus parasolitarius. Fastigioreticular fibers arise predominately from rostral regions of the FN, are entirely crossed and project mainly to: (1) medial regions of the nucleus reticularis gigantocellularis, (2) the dorsal paramedian reticular nucleus and (3) the magnocellular part of the lateral reticular nucleus. Fastigiopontine fibers, emerge with the UF, bypass the vestibular nuclei and terminate upon the contralateral dorsolateral pontine nuclei. Crossed fastigiospinal fibers separate from fastigiopontine fibers and descend in the ventrolateral tegmentum beneath the spinal trigeminal tract; in the medulla and upper cervical spinal cord these fibers are intermingled with those of the vestibulospinal tract. Fastigiospinal fibers terminate in the anterior gray horn at C-1 and probably descend further. Ascending fastigial projections arise from caudal parts of the FN, are entirely crossed and ascend in dorsal parts of the midbrain tegmentum. Label is transported bilaterally to the superior colliculi and the nuclei of the posterior commissure. Contralateral fastigiothalamic projections terminate in the ventral posterolateral (VPLc and VPLo) and in parts of the ventral lateral (VLo) thalamic nuclei. The major region of termination of fastigiothalamic fibers is in VPLo. Fastigiothalamic projections, probably conveying impulses concerned with equilibrium and somatic proprioception, appear to impinge upon thalamic neurons receiving inputs from less specialized receptors that signal information concerning position sense and body movement. More modest fastigial projections to VLo could directly influence activity of neurons in the primary motor cortex.     

Decreased muscarinic receptor binding in rat brain after paradoxical sleep deprivation: an autoradiographic study

Previous work demonstrated that paradoxical sleep deprivation (PSD) leads to a decrease in yawning behavior elicited by cholinergic agonists, suggesting that a downregulation of cholinergic muscarinic receptors may occur after PSD. More recent work using intracerebral injections of muscarinic agonists has suggested a critical role for M2 receptors in paradoxical sleep. In this study [³H]AF-DX 384 was used to investigate the effects of PSD on M2-type cholinergic receptors throughout the brain using quantitative autoradiography. After 96 h of paradoxical sleep deprivation, [³H]AF-DX 384 binding was generally reduced throughout the brain, and significantly so in the olfactory tubercle (−20%), n. accumbens (−23%), frontal caudate-putamen (−16%), islands of Callejas (−20%), piriform cortex (−24%), lateral (−26%) and medial (−24%) septum, anteromedial (−19%), ventrolateral (−22%), and lateral geniculate (−15%) nuclei of thalamus, deep layers of the superior colliculus (−15%), entorhinal cortex (−12%) and subiculum (−23%). [³H]AF-DX 384 binding was reduced in pontine structures, but not to a higher degree than in other brain areas. The observed downregulation of M2-type muscarinic receptors after PSD may be causally related to the previously reported decrease in cholinergically induced behaviors after PSD.     

AMPA receptor antagonism attenuates MK-801-induced hypermetabolism in the posterior cingulate cortex

The effect of pretreatment with an AMPA receptor antagonist, NBQX, on MK-801-induced alterations in glucose use was examined using [¹⁴C]-2-deoxyglucose autoradiography. NBQX (7 mg/kg) had minimal effect on glucose utilisation in all anatomical regions examined. The intravenous administration of MK-801 (0.2 mg/kg) induced increases in glucose use in the limbic system and cingulate cortex. MK-801 reduced glucose utilisation in the sensory motor and auditory cortices. Pretreatment with NBQX attenuated the MK-801-induced hypermetabolism in the posterior cingulate cortex. The decreases in glucose utilisation induced by MK-801 were not exacerbated by the pretreatment with NBQX. The interaction between NBQX and MK-801 suggests a possible method of attenuating some of the adverse effects of the non-competitive NMDA receptor antagonists in the posterior cingulate cortex.     

Dopamine D1 and D2 receptors in progressive supranuclear palsy: an autoradiographic study.

Dopamine D1 and D2 receptors were studied in brain tissue sections from a typical patient with progressive supranuclear palsy and in 7 age-matched brains. The density of D1 receptors in the caudate-putamen and frontal cortex of the patient was within control limits. By contrast, the density of nigral D1 receptors and striatal D2 receptors was dramatically reduced in the patient as compared to the control brains. This work shows again that the loss of striatal D2 receptors is the most plausible explanation for the poor response to dopaminergic drugs in patients with progressive supranuclear palsy. While the loss of nigral D1 receptors can be explained by the loss of nigral neurons, it seems that neurons bearing striatal D1 receptors are spared in progressive supranuclear palsy. The clinical effects of selective D1 agonists are worth testing in this devastating disorder.     

Dompamine receptors in the rat frontal cortex: an autoradiographic study.

Literature findings indicated that injection of low doses of [3H]spiperone results in a labelling of dopamine receptors in rat brain, but also in a labelling of serotonin receptors. Administration of pipamperone, a drug with serotonergic properties, to animals treated with [3H]spiperone reduced the serotonergic component of the binding and permitted an easier identification of dopamine receptor binding. At the level of Forceps Minor, there were elevated levels of receptors in the deeper layers of the cingulate cortex, in the region above the rhinal sulcus and in an area dorsal to the accumbens. This distribution is in agreement with the results of other biochemical, histochemical and electrophysiological studies.     

Postnatal changes in AMPA receptor regulation by phospholipase A2 treatment of synaptic membranes: temporally differential effects on agonist and antagonist binding.

Previous results have indicated that phospholipase A2 (PLA2) treatment of telencephalic membranes produced opposite effects on [3H]amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) binding in neonatal and adult rats. In the present study, we compared the effects of PLA2 treatment of telencephalic membranes on the binding characteristics of agonists and antagonists of the AMPA receptors in the developing rat brain. Whereas PLA2 treatment of telencephalic membranes from postnatal day (PND) 5 and 10 animals produced an important decrease in [3H]AMPA binding, the same treatment performed on PND 20, 25 and adult membranes resulted in a marked increase in [3H]AMPA binding; the shift from decreased to increased [3H]AMPA binding occurred at about PND 15. In contrast to [3H]AMPA binding, [3H]6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) binding was substantially reduced following PLA2 treatment at PND 5, 10 and 20, and effect due to a decrease in the maximal number of [3H]CNQX binding sites. In adult membranes, the effect of PLA2 treatment on [3H]CNQX binding was markedly reduced when compared to neonatal membranes. Pretreatment of synaptic membranes with PCMBS (a sulfhydryl reagent) increased [3H]AMPA binding in both young (PND 10) and adult telencephalic membranes, without significantly changing [3H]CNQX binding. The various effects of PLA2 treatment on agonist and antagonist binding did not appear to be due to major differences in the pharmacological properties of the AMPA receptors at different ages. The present results indicate that the characteristics of the binding sites for agonists and antagonists of the AMPA receptors are differentially modulated by the lipid environment during the postnatal period.(ABSTRACT TRUNCATED AT 250 WORDS)     

An autoradiographic study in mu-opioid receptor knockout mice

An autoradiographic study was carried out to study the opioid binding sites in a mu-opioid receptor knock-out mouse line whose exon 2 and 3 were deleted. Mu-opioid binding sites were undetectable in this knock-out mouse line while the binding of the other two types of receptors were unaltered. Our results suggest destroying functional mu-opioid receptor does not affect the expression of the other two opioid receptors.     

On the distribution of cholecystokinin receptor binding sites in the human brain: an autoradiographic study

Cholecystokinin (CCK) binding sites were localized by in vitro autoradiography in human postmortem brain materials from 12 patients without reported neurological diseases using [125I]Bolton-Hunter CCK octapeptide (BHCCK-8) as a ligand. The pharmacological characteristics of BHCCK-8 binding to mounted tissue sections were comparable to those previously reported in the rat. CCK-8 being the most potent displacer, followed by caerulein, CCK-4, and gastrin I. The distribution of BHCCK-8 binding sites was heterogeneous. These sites were highly concentrated in a limited number of gray matter areas and nuclei. The highest binding densities were seen in the glomerular and external plexiform layers of the olfactory bulb. BHCCK-8 binding sites were also enriched in the neocortex, where they presented a laminar distribution with low levels in lamina I, moderate concentration in laminae II to IV, high density in lamina V, and low levels in lamina VI. A different laminar distribution was seen in the visual cortex, where a low receptor density was observed in lamina IV but higher density in laminae II and VI. In the basal ganglia the nucleus accumbens, caudatus, and the putamen presented moderate to high densities of binding sites, while the globus pallidus lacked sites of BHCCK-8 binding. In the limbic system the only area presenting moderate to high density was the amygdaloid complex, particularly in the granular nucleus, while most of the thalamic nuclei were extremely poor or lacked BHCCK-8 binding. The hippocampal formation showed low (CA1-3) to moderate (subiculum) densities. Midbrain areas generally disclosed very low levels of BHCCK-8 binding sites. The pontine gray and the nucleus reticularis tegmenti pontis showed a relatively high density of CCK-8 receptor specific binding. Moderate to very high densities were found in few nuclei of the lower brainstem and spinal cord as the inferior olives and their accessory nuclei, the arcuate nuclei, the striae medullares, the efferent (motor) nucleus of the vagus, and the substantia gelatinosa of the cervical and thoracic spinal cord. These results are discussed in relation to the distribution of endogenous peptide and to the known physiological and pharmacological effects of substances acting on these receptors.     

Neurotransmitter receptor sites in human hippocampus: a quantitative autoradiographic study

The distribution of serotonin₁, cholinergic-muscarinic, α-adrenergic and opiate-type receptors was studied in the human hippocampus by quantitative autoradiography. Each receptor type exhibited a unique distribution. Serotonin₁ receptors were found to predominate in the subiculum, whereas α₁-adrenergic receptor are absent in that area and present at high levels in the dentate and the CA fields. High densities of muscarinic receptors appear in the subiculum and dentate gyrus. Opiate receptors are restricted to a medial aspect of the subiculum, with lower levels in the dentate and CA fields. The high anatomical resolution and quantitative character of the data may make it useful in the investigation of hippocampal pathology in humans.