Ovarian hormone effects on 5-hydroxytryptamine(2A) and 5-hydroxytryptamine(2C) receptor mRNA expression in the ventral hippocampus and frontal cortex of female rats

Alterations in female gonadal hormones are associated with anxiety and mood changes. The aim of the present study was to determine influences of chronic gonadal hormone supplementation on 5-HT(2A) and 5-HT(2C) receptor mRNA levels in the ventral hippocampus and the frontal cerebral cortex. Ovariectomized adult female Sprague-Dawley rats (n=37) received implantation of subcutaneous pellets containing different dosages of 17beta-estradiol alone or in combination with progesterone, or placebo pellets, for 2 weeks. Serotonin receptor mRNA levels were analyzed by in situ hybridization in the ventral hippocampus and 5-HT(2A) receptor mRNA also in the frontal cortex. Estradiol treatment in combination with low-dose progesterone increased 5-HT(2A) receptor mRNA by 43% in the CA2 region of the ventral hippocampus, while estradiol combined with high-dose progesterone increased the expression of this gene by 84% in ventral CA1. 5-HT(2A) mRNA expression in the frontal cortex was not influenced by hormone manipulation. 5-HT(2C) receptor gene expression was in the ventral hippocampus decreased in the CA2, ventral CA1 and the subiculum subregions by high-dose estradiol treatment (8-20% decreases). Effects on mood by gonadal hormones can be mediated, at least partly, through influences on 5-HT(2A) and 5-HT(2C) receptor expression.     

Muscarinic acetylcholine receptor subtype mRNA expression and ligand binding in the aged rat forebrain

Previous studies indicate that a 20-30% decline in muscarinic acetylcholine receptor binding occurs in localized areas of rat brain during aging. In this study, reduced [3H]-quinuclidinyl benzilate binding was observed in striata from 24-25-month-old rats relative to 5-6-month-old animals using homogenate binding assays. To determine if the decline in receptor concentration occurs as a result of decreased receptor synthesis, the expression of the m1, m3, and m4 muscarinic receptor mRNAs as well as [3H]-QNB binding were determined in adjacent sections of young and old male rats using in situ hybridization and in vitro receptor autoradiography respectively. A significant decline in collective muscarinic receptor binding as assessed by [3H]-QNB was observed in the caudate putamen, olfactory tubercle, nucleus accumbens, and several frontal and parietal cortical areas. The only difference observed in muscarinic mRNA expression for any of the three subtypes examined was a decline in m1 hybridization in the olfactory tubercle. The results of this study demonstrate that the regional brain areas displaying age-related decreases in receptor binding do not correlate with those areas showing a decrease in muscarinic receptor expression. Apparently, the decline in muscarinic acetylcholine receptor density with age does not result from a decline in receptor gene expression.     

Differential expression of muscarinic subtype mRNAs after exposure to neurotoxic pesticides

We have recently reported an increase in the density of muscarinic cholinergic receptors in mice neonatally exposed to a persistent environmental agent, dichlorodiphenyltrichloroethane (DDT), and a subsequent exposure as adults to nonpersistent toxicants, such as bioallethrin or paraoxon. Here we have examined the effects of an exposure like this on muscarinic receptor mRNA expression. Ten-day-old Naval Medical Research Institute mice received a single oral dose of DDT (0.5 mg/kg body weight). When aged 5 months, they received bioallethrin (0.7 mg/kg body weight per day for 7 days) or paraoxon (1.4 mg/kg body weight every second day for 7 days). mRNA expression of subtypes m1, m3, and m4 was studied in 7-month-old animals. Changes could only be discovered in the DDT-bioallethrin treated mice, where expression of subtype m4 was elevated in cortex and caudate putamen. Moreover, the expression pattern of the subtypes m1, m3, and m4 in mouse brains was found to be very similar to that seen in rats, except for slight differences in the pyramidal cell layer of the hippocampus, where the outermost part of the CA3 region did not show any m4 hybridization. The present study indicates that the earlier observed increase in muscarinic receptor density in mice exposed as neonates to DDT and as adults to bioallethrin can be attributed to changes in the expression of m4.     

Localization of the m5 muscarinic cholinergic receptor in rat circle of Willis and pial arteries

The expression and microanatomical localization of the muscarinic cholinergic m5 receptor subtype was investigated in rat circle of Willis and pial arteries by in situ hybridization, immunoblotting and immunohistochemistry. In situ hybridization histochemistry revealed a strong signal in the endothelium of circle of Willis and pial arteries and a moderate signal in the tunica media of the same arteries, within smooth muscle. Exposure of membranes of arteries to anti-m5 receptor protein antibodies caused the development of a band of approximately 81 kDa. Immunohistochemistry revealed the accumulation of m5 receptor protein immunoreactivity primarily within endothelium of circle of Willis and cerebral arteries and to a lesser extent in the tunica media, within smooth muscle. Medium (external diameter 200-100 microm) and small-sized (external diameter smaller than 100 microm) pial arteries displayed a significantly higher immune staining than large-sized pial arteries or circle of Willis arteries. The above data that are consistent with recent functional studies reporting cholinergic dilation of cerebral blood vessels mediated via a m5 receptor, have shown that both endothelial and muscular components of cerebral arteries synthesize and express a muscarinic m5 receptor. In view of the peculiar localization in cerebral vessels, handling of the muscarinic m5 receptor may be considered as an approach in the treatment of cerebrovascular disease.     

Evidence for novel estrogen binding sites in the rat hippocampus

Estrogen modulates the morphology and physiology of the rat hippocampus and enhances cognitive function. While estrogen receptor (alpha and beta) messenger RNAs have been detected in the hippocampus, the presence of functional protein remains uncertain. The present study used a new radiolabeled estrogen, [125I]estrogen, and in vivo autoradiography to address this question. Nuclear uptake and retention of [125I]estrogen was detected in the pyramidal cells of CA1-CA3, with the majority of cells in the ventral horn of CA2 and CA3 being labeled. Additional labeled cells were scattered throughout the strata oriens and radiatum and the hilus of the dentate gyrus. Since the number and distribution of labeled cells in the hippocampus was more than expected, in situ hybridization was used to assess the localization of estrogen receptor (alpha and beta) messenger RNAs in this brain region. The results revealed that both estrogen receptors are expressed in regions where [125I]estrogen binding was seen, although the intensity of estrogen receptor-alpha hybridization signal appears to be stronger when compared with estrogen receptor-beta.The results of these studies have demonstrated the presence of estrogen receptors in rat hippocampus and shown that the distribution of binding sites was much greater than expected, particularly in the pyramidal cells of the ventral hippocampus. These observations challenge our current thinking about steroid hormones and their mechanism(s) of action in a region associated with learning and memory and affected by the neurodegenerative conditions of aging.     

Muscarinic cholinergic receptor subtypes in the hippocampus of aged rats.

In spite of the suggestion of impaired muscarinic function in adult-onset cognitive disorders, data on the expression of muscarinic receptors in the hippocampus as a function of age are inconsistent. One reason may be that the majority of investigations were unable to differentiate the five brain muscarinic receptors subtypes. In this study, using a protocol based on a combination of both kinetic and equilibrium binding approaches, we have assessed the expression and the density of M1-M5 muscarinic cholinergic receptors in the hippocampus of Fisher 344 rats aged 6, 15 and 22 months. An age-related decrease of the density of M1 receptor was found in pyramidal neurons of the CA1 subfield. In this area, other subtypes of muscarinic receptors were unchanged with the exception of a loss of M2 receptor in the radial layer. In the CA3 subfield, receptor changes involved M2, M3 and M5 subtypes, whereas in the dentate gyrus, the main changes affected M1 and M2 receptors of the granular layer and M2 and M3 receptors of the molecular layer. The above findings indicate that analysis of age-related changes of different muscarinic cholinergic receptors might represent a useful contribution to identifying the basis of cholinergic neurotransmission impairment in adult-onset cognitive dysfunction.     

Light-microscopic distribution and parasagittal organisation of muscarinic receptors in rabbit cerebellar cortex

Recent studies on the effects of intrafloccular injections of muscarinic agonists and antagonists on compensatory eye movements in rabbit, indicate that muscarinic receptors may play a modulatory role in the rabbit cerebellar circuitry. It was previously demonstrated by Neustadt et al. (1988), that muscarinic receptors in rabbit cerebellar cortex are distributed into alternating longitudinal zones of very high and very low receptor density. In the present study, the zonal and cellular distribution of muscarinic receptors in the rabbit cerebellar cortex is investigated in detail using in vitro ligand autoradiography with the non-selective high-affinity antagonist [³H]quinuclidinyl benzilate (QNB), and the M2-specific antagonist [³H]AF-DX384, and immunocytochemistry with a monoclonal antibody specific for the cloned m2 muscarinic receptor protein. [³H]QNB and [³H]AF-DX384 binding sites and m2-immunoreactivity had similar overall distributions: dense labeling occurred in the dendritec arbors of a subset of Purkinje cells that are organized into parasagittal bands. A high level of muscarinic receptor labeling was also observed in a thin substratum of the molecular layer immediately above the Purkinje cell layer of the vestibulo-cerebellar lobules, i.e. the nodulus, the ventral uvula and the flocculus. Labeling in this stratum was associated with densely packed fibres, which were putatively identified as parallel fibres. Also Golgi cells, which were localized in part in the molecular layer, and a subset of mossy fibre rosettes, primarily concentrated in lobule VI, were immunoreactive for the m2 receptor. The parasagittal bands of labeled Purkinje cell dendrites were most prominent in the anterior lobe (lobules I–V), in crus 1 and 2, in the flocculus, the ventral paraflocculus and the rostral folium of the nodulus. In other lobules, only infrequent Purkinje cells contained muscarinic receptors. The parasagittal organisation of muscarinic receptors differed from that of zebrin I, a Purkinje cell-specific protein which is often used as a marker of parasagittal parcelation of the cerebellar cortex. In the anterior lobe, however, there was a partial correspondence between muscarinic receptor and zebrin I bands. In the flocculus the distribution of muscarinic-receptor-positive Purkinje cells was related to the distinct white matter compartments as revealed with acetylcholinesterase (AChE) histochemistry. Muscarinic receptor-containing Purkinje cells were located primarily in the floccular zone 1, which is implicated in the control of eye movements about a horizontal axis. In order to relate the distribution of muscarinic receptor labeling to that of cholinergic nerve terminals, [³H]QNB binding sites and sodium-dependent [³H]hemicholinium-3 binding were compared. Sodium-dependent [³H]hemicholinium-3 binding sites mainly occurred in the granule cell layer of the vestibulo-cerebellum, which corresponds well with the distribution of the acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT). However, sodium-dependent [³H]hemicholinium binding complemented, rather than co-localized with, muscarinic receptors which were primarily distributed in the molecular layer of the lobules of the vestibulo-cerebellar lobules. Their functional significance is puzzling, since their distribution does not correspond to that of markers of cholinergic innervation.     

Modulation of low-threshold T-type calcium channels by the five muscarinic receptor subtypes in NIH 3T3 cells

The modulation of a transient T-type calcium current by the five muscarinic receptor subtypes, stably expressed in NIH 3T3 cells, was studied with the whole-cell patch-clamp technique. Voltage-step depolarizations applied to the NIH 3T3 cells revealed a low-voltage-activated (LVA) T-type calcium current that was inhibited by Ni2+ and unaffected by omega-conotoxin GVIA. In cells transfected with the m3 and m5 muscarinic receptors, application of acetylcholine (ACh) resulted in a pertussis-toxin-insensitive increase in peak T-type calcium current amplitude. The m3-induced atropine-sensitive increase in current amplitude was accompanied by a shift in the voltage dependence of activation to more hyperpolarized potentials. The increase in peak T-type calcium current amplitude and the shift in voltage dependence was mimicked by incubation with 500 microM 8-bromo-cAMP. Conversely, T-type calcium current amplitudes were reduced by incubation with 10 microM RpcAMPS, an inhibitor of cAMP-dependent protein kinase (PKA). Preincubation with 500 microM 8-bromo-cAMP or with 10 microM RpcAMPS abolished the increase in T-type calcium current amplitude previously noted on stimulation of the m3 muscarinic receptor by ACh. Application of ACh to NIH 3T3 cells stably transformed with the m1 muscarinic receptor resulted in no discernable change in T-type calcium current amplitude. However, on pre-incubation of the cells with calphostin C, an inhibitor of protein kinase C (PKC), application of ACh to the cells now resulted in a robust increase in T-type calcium current amplitude. Application of 500 nM PDBu, an activator of PKC, reduced the T-type calcium current amplitude. No significant changes in T-type calcium currents were observed on application of ACh to cells stably transfected with the m2 or m4 muscarinic receptors. However, after pre-incubation with forskolin, the m2 muscarinic receptor induced a decrease in T-type calcium current amplitude. Stimulation of the ml, m3 and m5 muscarinic receptors in the NIH 3T3 cell resulted in dose-dependent increases in the concentration of intracellular cAMP in comparison to control as determined by cAMP immunoassay. Conversely, stimulation of the m2 and m4 muscarinic receptors by carbachol resulted in a dose-dependent reduction in intracellular concentrations of cAMP, as compared with control basal levels. It is concluded that the m3 and m5 muscarinic receptors enhance T-type calcium channel activity. At least in the case of the m3 muscarinic receptor, the increased T-type channel activity appeared to be mediated via increased cAMP levels and subsequent activation of PKA. The lack of effect of the ml muscarinic receptor on the T-type calcium channel was probably due to the opposing actions of concomitant activation of both PKC and PKA. The physiological significance of these findings is discussed.     

Regional heterogeneity in the distribution of neurotransmitter markers in the rat hippocampus.

A detailed neurochemical analysis of the distribution of markers for the most relevant neurotransmitter systems within the rat hippocampal formation has been performed. The hippocampi, obtained from unfrozen brains of male Sprague-Dawley rats were subdissected into tissue parts containing mainly CA1, CA3 or the dentate gyrus, respectively. Each part was further divided into ventral and dorsal halves. In these six hippocampal subregions the concentrations of noradrenaline, dopamine, serotonin, 3-methoxy-4-hydroxyphenylglycol, 5-hydroxyindoleacetic acid and the putative neurotransmitter amino acids glutamate, aspartate, GABA, glycine and taurine, and the levels of somatostatin and neuropeptide Y and the activities of choline acetyltransferase, acetylcholinesterase and glutamate decarboxylase were measured. A marked heterogeneity in the subregional distribution of markers for various neurotransmitter systems within the hippocampal formation was observed. Each neuronal marker was characterized by an individual pattern of distribution. Most of the markers showed a concentration-gradient, increasing from dorsal to ventral; only taurine was more abundant in the dorsal than in the ventral parts and no dorsoventral difference was seen for aspartate, glycine and neuropeptide Y. The highest molar ratios of total 3-methoxy-4-hydroxyphenylglycol to noradrenaline and 5-hydroxyindoleacetic acid to serotonin were found in the dorsal hippocampus. The levels of noradrenaline, GABA and glutamate decarboxylase activity were highest in the dentate gyrus and lowest in CA1. The concentrations of somatostatin were highest in CA1; those of serotonin were highest in CA3. Highest activities of choline acetyltransferase and acetylcholinesterase were found in the dentate gyrus; lowest activities were found in CA3. In CA3 the lowest values of glutamate, aspartate, taurine and somatostatin were also found. The heterogeneity in the distribution of individual neurochemical markers allows insights into possible functional differences of hippocampal subregions and provides a relevant basis for future neurochemical investigations in this brain area.     

Differential expression of NMDA and AMPA receptor subunits in rat dorsal and ventral hippocampus

Several studies have demonstrated anatomical and functional segregation along the dorsoventral axis of the hippocampus. This study examined the possible differences in the AMPA and NMDA receptor subunit composition and receptor binding parameters between dorsal and ventral hippocampus, since several evidence suggest diversification of NMDA receptor-dependent processes between the two hippocampal poles. Three sets of rat dorsal and ventral hippocampus slices were prepared: 1) transverse slices for examining a) the expression of the AMPA (GluRA, GluRB, GluRC) and NMDA (NR1, NR2A, NR2B) subunits mRNA using in situ hybridization, b) the protein expression of NR2A and NR2B subunits using Western blotting, and c) by using quantitative autoradiography, c(1)) the specific binding of the AMPA receptor agonist [(3)H]AMPA and c(2)) the specific binding of the NMDA receptor antagonist [(3)H]MK-801, 2) longitudinal slices containing only the cornus ammonis 1 (CA1) region for performing [(3)H]MK-801 saturation experiments and 3) transverse slices for electrophysiological measures of NMDA receptor-mediated excitatory postsynaptic potentials. Ventral compared with dorsal hippocampus showed for NMDA receptors: 1) lower levels of mRNA and protein expression for NR2A and NR2B subunits in CA1 with the ratio of NR2A /NR2B differing between the two poles and 2) lower levels of [(3)H]MK-801 binding in the ventral hippocampus, with the lowest value observed in CA1, apparently resulting from a decreased receptor density since the B(max) value was lower in ventral hippocampus. For the AMPA receptors CA1 our results showed in ventral hippocampus compared with dorsal hippocampus: 1) lower levels of mRNA expression for GluRA, GluRB and GluRC subunits, which were more pronounced in CA1 and in dentate gyrus region and 2) lower levels of [(3)H]AMPA binding. Intracellular recordings obtained from pyramidal neurons in CA1 showed longer NMDA receptor-mediated excitatory postsynaptic potentials in ventral hippocampus compared with dorsal hippocampus. In conclusion, the differences in the subunit mRNA and protein expression of NMDA and AMPA receptors as well as the lower density of their binding sites observed in ventral hippocampus compared with dorsal hippocampus suggest that the glutamatergic function differs between the two hippocampal poles. Consistently, the lower value of the ratio NR2A/NR2B seen in the ventral part would imply that the ventral hippocampus NMDA receptor subtype is functionally different than the dorsal hippocampus subtype, as supported by our intracellular recordings. This could be related to the lower ability of ventral hippocampus for long-term synaptic plasticity and to the higher involvement of the NMDA receptors in the epileptiform discharges, observed in ventral hippocampus compared with dorsal hippocampus.     

Muscarinic acetylcholine neurotransmission enhances the late-phase of long-term potentiation in the hippocampal-prefrontal cortex pathway of rats in vivo: a possible involvement of monoaminergic systems

The prefrontal cortex is continuously required for working memory processing during wakefulness, but is particularly hypoactivated during sleep and in psychiatric disorders such as schizophrenia. Ammon's horn CA1 hippocampus subfield (CA1) afferents provide a functional modulatory path that is subjected to synaptic plasticity and a prominent monoaminergic influence. However, little is known about the muscarinic cholinergic effects on prefrontal synapses. Here, we investigated the effects of the muscarinic agonist, pilocarpine (PILO), on the induction and maintenance of CA1-medial prefrontal cortex (mPFC) long-term potentiation (LTP) as well as on brain monoamine levels. Field evoked responses were recorded in urethane-anesthetized rats during baseline (50 min) and after LTP (130 min), and compared with controls. LTP was induced 20 min after PILO administration (15 mg/kg, i.p.) or vehicle (NaCl 0.15 M, i.p.). In a separate group of animals, the hippocampus and mPFC were microdissected 20 min after PILO injection and used to quantify monoamine levels. Our results show that PILO potentiates the late-phase of mPFC LTP without affecting either post-tetanic potentiation or early LTP (20 min). This effect was correlated with a significant decrease in relative delta (1-4 Hz) power and an increase in sigma (10-15 Hz) and gamma (25-40 Hz) powers in CA1. Monoamine levels were specifically altered in the mPFC. We observed a decrease in dopamine, 5-HT, 5-hydroxyindolacetic acid and noradrenaline levels, with no changes in 3,4-hydroxyphenylacetic acid levels. Our data, therefore, suggest that muscarinic activation exerts a boosting effect on mPFC synaptic plasticity and possibly on mPFC-dependent memories, associated to monoaminergic changes.     

Muscarinic M2 receptor mRNA expression and receptor binding in cholinergic and non-cholinergic cells in the rat brain: a correlative study using in situ hybridization histochemistry and receptor autoradiography.

The goal of the present study was to identify the cells containing mRNA coding for the m2 subtype of muscarinic cholinergic receptors in the rat brain. In situ hybridization histochemistry was used, with oligonucleotides as hybridization probes. The distribution of cholinergic cells was examined in consecutive sections with probes complementary to choline acetyltransferase mRNA. Furthermore, the microscopic distribution of muscarinic cholinergic binding sites was examined with a non-selective ligand ([3H]N-methylscopolamine) and with ligands proposed to be M1-selective ([3H]pirenzepine) or M2-selective ([3H]oxotremorine-M). The majority of choline acetyltransferase mRNA-rich (i.e. cholinergic) cell groups (medial septum-diagonal band complex, nucleus basalis, pedunculopontine and laterodorsal tegmental nuclei, nucleus parabigeminalis, several motor nuclei of the brainstem, motoneurons of the spinal cord), also contained m2 mRNA, strongly suggesting that at least a fraction of these receptors may be presynaptic autoreceptors. A few groups of cholinergic cells were an exception to this fact: the medial habenula and some cranial nerve nuclei (principal oculomotor, trochlear, abducens, dorsal motor nucleus of the vagus). Furthermore, m2 mRNA was not restricted to cholinergic cells but was also present in many other cells throughout the rat brain. The distribution of m2 mRNA was in good, although not complete, agreement with that of binding sites for the M2 preferential agonist [3H]oxotremorine-M, but not with [3H]pirenzepine binding sites. Regions where the presence of [3H]oxotremorine-M binding sites was not correlated with that of m2 mRNA are the caudate-putamen, nucleus accumbens, olfactory tubercle and islands of Calleja. The present results strongly suggest that the M2 receptor is expressed by a majority of cholinergic cells, where it probably plays a role as autoreceptor. However, many non-cholinergic neurons also express this receptor, which would be, presumably, postsynaptically located. Finally, comparison between the distribution of m2 mRNA and that of the proposed M2-selective ligand [3H]oxotremorine-M indicates that this ligand, in addition to M2 receptors, may also recognize in certain brain areas other muscarinic receptor populations, particularly M4.     

Midbrain muscarinic receptors modulate morphine-induced accumbal and striatal dopamine efflux in the rat

Midbrain dopamine neurons are critical in mediating the rewarding effects of opiates in dependent rats, as well as modulating some manifestations of opiate withdrawal. Morphine is known to excite dopamine neurons and thereby facilitate forebrain dopamine transmission through inhibition of GABA neurons. Cholinergic neurons in the mesopontine laterodorsal and pedunculopontine tegmental nuclei provide the principal source of excitatory cholinergic input to ventral tegmental area and substantia nigra pars compacta dopamine-containing neurons, via actions on midbrain muscarinic and nicotinic acetylcholine receptors. The present study hypothesized that a reduction in tonic cholinergic input via blockade of midbrain muscarinic receptors would reduce the pharmacological effects of morphine on forebrain dopamine release. Using in vivo chronoamperometry, alterations in morphine-evoked dopamine efflux were monitored at stearate-graphite paste electrodes implanted unilaterally in the nucleus accumbens and striatum of urethane (1.5 g/kg) anesthetized rats, following the pharmacological inhibition of ventral tegmental area/substantia nigra pars compacta muscarinic receptors. The facilitatory effects of morphine (2.0 mg/kg, i.v.) on accumbens and striatal dopamine efflux were markedly reduced by prior infusion of the non-selective muscarinic receptor antagonist scopolamine (200 microg/microl) into the ventral tegmental area or substantia nigra pars compacta, respectively. These findings demonstrate that decreased activation of midbrain muscarinic receptors attenuates the excitatory effects of morphine on mesoaccumbens and nigrostriatal dopaminergic transmission.     

The bite-raised condition enhances the aging process in the dorsal and ventral hippocampus

The bite raised condition decreases the number of neurons and increases the amount of glial fibrillary acidic protein in the hippocampus of aged SAMP8 mice. In the present study, we examined whether these effects differ between the dorsal and ventral hippocampus. In bite-raised SAMP8 mice, the number of neurons was significantly lower in the hippocampal CA1 and dentate gyrus (DG) subfields compared to control mice. In the bite raised condition, the number of neurons was significantly lower in both the dorsal and ventral CA3 subfields, and the number of glial fibrillary acidic protein-labeled astrocytes was increased in the CA1, CA3, and DG subfields, compared to control mice. These data suggest that in aged SAMP8 mice, the bite-raised condition enhanced aging processes in both the dorsal and ventral hippocampus.     

树内侧隔核—斜角带复合体向腹侧海马的胆碱能和非胆碱能投射

本研究运用 WGA-HRP逆行追踪结合胆碱乙酰化酶免疫组织化学法研究了树鼠句内侧隔核 -斜角带复合体向腹侧海马的投射。结果表明 ,(1)树鼠句腹侧海马接受内侧隔核 -斜角带复合体的投射有三种形式 ,即来自内侧隔核 ,内侧隔核 -斜角带垂直部的外侧部和内侧隔核 -斜角带垂直部的后部。(2 )腹侧海马来自内侧隔核和斜角带垂直部的投射主要是非胆碱能的 ,其非胆碱能和胆碱能均主要来自内侧隔核。 (3 )腹侧海马各亚区 (CA1、CA2 /CA3和齿状回门区或 CA4)都主要接受内侧隔核的纤维传入 ,但胆碱能和非胆碱能比例不同 ,CA1、CA2 /CA3和 CA4来自内侧隔核 -斜角带垂直部的投射均主要是非胆碱能的 ,且主要来自内侧隔核 ,其胆碱能几乎等量来自内侧隔核和斜角带垂直部。内侧隔核 -斜角带复合体—腹侧海马亚区胆碱能和非胆碱能投射比例的不同 ,为认识内侧隔核 -斜角带复合体—海马通路对记忆环路中的海马调节机制 ,提供了新的形态学依据     

Effects of ventral hippocampal long-term potentiation and depression on the gamma-band local field potential in anesthetized rats

We examined the effect of long-term potentiation or depression (LTP or LTD) on the local field potential, focusing on the gamma-band (40–100 Hz) power, in the ventral hippocampus CA1 of anesthetized rats. LTP and LTD induction in the CA3–CA1 pathway increased the CA1 spontaneous gamma-band power by around 40 and 80–100 Hz, respectively, while neither changed the evoked levels significantly. These results suggest that the ventral CA1 local field potential can maintain bidirectional plasticity in the steady state for the long term. Given the involvement of synaptic plasticity in learning and memory, the gamma-band power change associated with LTP/LTD may relate to ventral hippocampal functions. The LTP increased the spontaneous power at around 40 Hz of the gamma-band frequency in the ventral CA1, and the LTD did the same at 80–100 Hz. The biphasic increase may distribute the subsequent input appropriately to regulate the relevant synaptic history in the ventral CA1 and anatomically related structures in vivo.     

Histochemical demonstration and mapping of 5-hydroxytryptamine- and catecholamine-containing neuron systems in the human fetal brain

Summary The distribution of monoamine neurons in the human fetal brain was studied by Falck-Hillarp fluorescence histochemistry. Catecholamine (CA)- and 5-hydroxytryptamine (5-HT)-neuron systems were found in the smallest brain studied, obtained from an embryo having a total length of 2.1 cm and a gestational age of 7 weeks. A marked proliferation and differentiation of the monoamine neuron systems took place between the 7th and 23rd week of gestation (the range covered in the present investigation) permitting a mapping of major cell groups, as well as several axon pathways and terminal innervation patterns.The basic cytoarchitectonic features of the central monoamine neurons in human fetuses were strikingly similar to those of the fetal rat. Thus, a large complex of cell bodies was found in the developing substantia nigra area, in all probability the CA neurons of the nigro-striatal dopamine system. Axons projected towards the corpus striatum. Here, the putamen and, somewhat later, the caudate nucleus became richly innervated by CA nerve terminals. Small clusters of CA nerve cells were found in the hypothalamus, e. g. in the ventral periventricular area.5-hydroxytryptamine nerve cell bodies were distributed throughout the raphe areas from the medulla oblongata to the mesencephalon forming several well delineated groups, e.g. a large group in the area of nuc. raphe dorsalis. 5-HT axons projected caudally in the ventral parts of the medulla oblongata and into the spinal cord and rostrally through the mesencephalon and into the forebrain.CA cell bodies were also found in several large complexes of the medulla oblongata and pons, where such cell bodies are of the noradrenaline type in animals. The principal locus coeruleus consisted of densely packed fluorescent cells and several loosely packed groups extended laterally, medially, dorsally and rostrally from this area. Several axon bundles ascended dorsally from this complex. Ventrally and dorsally located CA cell groups were found in the medulla oblongata, and green fluorescent axons descended into the spinal cord.Varicose nerve terminals of the CA type were found, e.g. in the spinal cord, around the third ventricle and, using brain smears, also in the developing cerebral and cerebellar cortices.There seemed to be an outflow of CA axons in ventral nerve roots of cranial and spinal nerves. The developing pineal gland showed scattered 5-HT-containing parenchymal cells. Area postrema contained a number of strongly fluorescent CA cells and some weaker fluorescent 5-HT cells.