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Innervation of the amygdaloid complex by catecholaminergic cell groups of the ventrolateral medulla.

The projections to the amygdaloid complex (AMG), originating in the catecholaminergic cell groups of the ventrolateral medulla (VLM), were studied in the rat by using either the retrograde tracer fluoro-gold (FG) or the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) in combination with tyrosine hydroxylase (TH) and/or phenylethanolamine-N-methyltransferase (PNMT) immunohistochemistry. In the first series of experiments, injections of FG were made into regions of the central nucleus of the amygdala (ACe) where dense TH and PNMT immunoreactivity was previously observed, and then sections of the brainstem were processed for TH and PNMT immunoreactivity. FG retrogradely labelled neuronal cell bodies were observed throughout the rostrocaudal extent of VLM, bilaterally, with a contralateral predominance. Approximately 44% of the FG labelled cell bodies in VLM were also immunoreactive to the catecholamine biosynthetic enzymes TH and/or PNMT. Most of these catecholaminergic neurons were part of the A1 noradrenergic cell group in the caudal VLM and to a lesser extent part of the C1 adrenergic cell group in the rostral VLM. In the second series of experiments, PHA-L was iontophoresed into VLM at different rostrocaudal levels where in the previous series of experiments FG retrogradely labelled cell bodies were observed. Transverse sections of the forebrain and brainstem were then processed for the demonstration of PHA-L and either TH or PNMT immunoreactivity in cell bodies, axons, and presumptive axon terminals. PHA-L injection sites within either the caudal or rostral VLM resulted in labelled axons and terminal bouton-like swellings primarily in the contralateral AMG and to a lesser extent in the ipsilateral AMG. The ACe was observed to receive the greatest innervation from either VLM site. Additionally, PHA-L labelled fibers and presumptive terminal boutons were observed within the intercalated, medial, basomedial, and basolateral nuclei of the AMG. Most of the PHA-L labelled fibers and presumptive terminal boutons in the AMG after a caudal VLM (A1 region) injection also displayed TH immunoreactivity, whereas after a PHA-L injection into the rostral VLM (C1 region) all of the labelled axons and axon terminals in the AMG also were immunoreactive to PNMT. These data demonstrate that catecholaminergic neurons in A1 and C1 regions of VLM innervate the AMG and suggest that these VLM neurons may be involved in relaying afferent information directly to the AMG which influences the activity of AMG neurons controlling autonomic, endocrine, and behavioural functions.

Afferent Pathways↗

Dopamine, noradrenaline and 3,4-dihydroxyphenylacetic acid (DOPAC) levels of individual brain nuclei, effects of haloperidol and pargyline.

Noradrenaline (NA), dopamine (DA) and DOPAC were determined with a newly developed radioenzymatic method simultaneously in the striatum, limbic system, hypothalamus and in catecholamine-containing cell groups of the rat brain. Only a loose relationship could be established between DOPAC and DA contents in the various brain areas. The lowest relative DOPAC level (DOPAC/DA ratio) was found in the median emience, while it was the highest in the periventricular nucleus of the hypothalamus. Haloperidol increased the DOPAC level in only part of the nuclei examined (striatum, olfactory tubercle, central amygdaloid nucleus), while in other limbic regions as well as in the hypothalamic dorsomedial, arcuate and paraventricular nuclei it proved to be ineffective. The DOPAC level in the locus coeruleus was decreased by haloperidol. Pargyline caused an appr. 50% decrease of DOPAC content of most of the nuclei in 10 min; the effectivity of the drug did not show parallelism with that of haloperidol. The monoamine oxidase inhibition caused no change in the DOPAC level in the hypothalamic periventricular and paraventricular nuclei. Results are discussed as a consequence of different reactivity of various DA-ergic terminals and catecholamine cell bodies to haloperidol and pargyline.

3,4-Dihydroxyphenylacetic Acid↗

Detailed mapping of CGRP mRNA expression in the rat central nervous system: comparison with previous immunocytochemical findings.

The localization of CGRP mRNA in neurons of the rat brain and spinal cord was assessed by in situ hybridization histochemistry (ISH) using a radiolabeled synthetic 57-mer oligodeoxynucleotide probe complementary to the rat prepro CGRP mRNA. Results were compared with previously published findings of CGRP-immunoreactive (CGRP-IR) cell bodies revealed by an indirect immunofluorescence technique. The highest numbers of CGRP mRNA expressing neurons as well as the greatest intensity of staining were found in the lateral hypothalamic area, the parabrachial nuclei, and among the cranial motor nuclei, especially in the nuclei of the 7th and 12th nerve and the ambiguus nucleus, which is generally in good agreement with findings assessed by immunocytochemistry (ICH). However, some mismatches between the localization of the peptide by ICH and the localization of the CGRP mRNA were also observed. Thus, ISH was not able to confirm CGRP-IR in cells of the amygdaloid complex and parts of the medial hypothalamus, the central gray, and the inferior colliculus, but ISH revealed considerably more CGRP mRNA expressing cells in the lateral hypothalamic area, arcuate nucleus, posterior and peripeduncular thalamic nuclei, and all cranial motor nuclei than CGRP-IR containing cells found by ICH. Moreover, ISH also revealed CGRP mRNA synthesis in the nucleus of the lateral olfactory tract and in the perihypoglossal nuclei that were devoid of CGRP-IR. The reasons for the observed mismatches still remain to be elucidated; however, intracerebroventricular colchicine pretreatment used to increase immunocytochemical signals also might have induced or suppressed gene expression in certain brain regions in an unpredictable matter. On the other hand, detection of only the mRNA in a certain region does not necessarily mean that also the active peptide is synthesized there.

Animals↗

Fine structural organization of the ependymal region of the paraventricular nucleus of the rat thalamus and its relation with projection neurons.

The ependymal lining of the diencephalic third ventricle is known to exhibit significant variation in zonal architecture and the relations of neurites to the ventricular surface in different regions remains obscure. The present study explores the fine structural organization of the ependymal region of the thalamic paraventricular nucleus. Methodology was developed for tracing neurites of cells retrogradely labelled with horseradish peroxidase based on our recent observation that paraventricular neurons projecting to the amygdaloid complex cluster near the ventricle and emit numerous dendrites extending toward the ependymal surface. A relatively uniform population of cuboidal 'pale' ependymocytes dominates the ventricular lining of the thalamic paraventricular nucleus, although a few 'dark' ependymocytes are interspersed. The subependymal region displays a variety of glial elements. Dendrites of thalamic paraventricular projection neurons terminate in proximity to the ependymal layer from which they are generally separated by thin cytoplasmic processes of putative astrocytes, and few indent the basal portion of ependymal cells. Thin 'terminal' (i.e., serially traced) horseradish peroxidase-labelled dendrites filled with lipid and lysosome-like dense bodies were often enveloped by astrocyte membrane whorls. This feature may constitute a reactive glial response in horseradish peroxidase-labelled dendritic terminals. A distinctive arrangement of tortuous astrocyte leaflets was insinuated between the basal portion of ependymocytes in a zone exhibiting numerous caveolae, apparently isolating neurites from direct contact with the cerebrospinal fluid. These findings indicate that the ependymal region of the thalamic paraventricular nucleus is not characterized by those features of the basal third ventricle suspected to confer neuroendocrine interaction between neurons and cerebrospinal fluid. The structural arrangement between ependymocytes and thalamic paraventricular projection cells indicate a specialized relation of these neurons with the ependymal interface, but apparently not directly with the overlying cerebrospinal fluid.

Animals↗

Correlation between reactive sprouting and microtubule protein expression in epileptic hippocampus.

Temporal lobe epilepsy in both human and rats is associated with a collateral sprouting of hippocampal mossy fibers (i.e. the axons of granule cells). This sprouting generates abnormal recurrent synaptic connections. We previously showed that in the experimental model of temporal lobe epilepsy induced by an intra-amygdaloid injection of kainate, the synaptic remodeling of mossy fibers was preceded by a transient increased expression of alpha-tubulin in granule cells. This suggests that an overproduction of tubulin polymers may be responsible, at least in part, for the elongation and side-branching of mossy fibers, which occurs 12-30 days after seizures. In the present study we show that this increased expression of alpha-tubulin is accompanied by an increased expression of the microtubule-associated proteins MAP2 and TAU. Thus, using in situ hybridization, we observe that MAP2 messenger RNA levels increased in granule cell bodies and dendrites from day 3 to two weeks after kainate treatment. This rise is associated with a concomitant transient increase of MAP2 immunoreactivity in the granule cell dendrites. TAU messenger RNA also increases in granule cell bodies, while TAU immunoreactivity increases in their axons, the mossy fibers. The time course of these changes parallels that of alpha-tubulin, and develops before and during the axonal mossy fiber sprouting. Since MAP2 and TAU are important for the initiation, elongation and stabilization of neurites, we suggest that the overexpression of these proteins via the formation of microtubules may play an important role in the sprouting of mossy fibers in epileptic rats.

Amygdala↗

Amygdala functions within the alimentary system.

The amygdaloid complex plays an important role in various defensive, sexual and metabolic functions of the organism. Our previous experiments on the defensive functions demonstrated that the amygdala may be divided into dorsomedial excitatory and basolateral inhibitory parts. Our recent experiments showed that this division is true also for alimentary mechanisms. The dorsomedial part of the amygdala acts as a facilitatory "center" and the lateral part as an inhibitory alimentary "center". These functions of the amygdala are parallel to those of the hypothalamic feeding centers. Bilateral damage to either the dorsomedial amygdala or to the lateral hypothalamus produced aphagia with adipsia, decrease of body weight and impairment of both classical and instrumental reactions. These changes were accompanied by low general arousal, atonia, catatonic like positions, negavitism and loss of positive emotional reactions. Damage to the lateral amygdala, on the other hand, produces a syndrome similar to damage to the ventromedial hypothalamus, i.e. hyperphagia and an increase of body weight. Slight increase of both classical and instrumental reactions and disinhibition of responses during intertrial intervals were found in both cases. Combined damage of the dorsomedial amygdala and lateral hypothalamus enhanced the symptoms attributable to each and prolonged the period of aphagia. Damage to the lateral amygdala subsequent to lesions of the dorsomedial amygdala and/or the lateral hypothalamus produced restoration of food intake, instrumental reactions and general arousal.

Amygdala↗

Expression without recognition: contributions of the human amygdala to emotional communication.

A growing body of evidence from humans and other animals suggests the amygdala may be a critical neural substrate for emotional processing. In particular, recent studies have shown that damage to the human amygdala impairs the normal appraisal of social signals of emotion, primarily those of fear. However, effective social communication depends on both the ability to receive (emotional appraisal) and the ability to send (emotional expression) signals of emotional state. Although the role of the amygdala in the appraisal of emotion is well established, its importance for the production of emotional expressions is unknown. We report a case study of a patient with bilateral amygdaloid damage who, despite a severe deficit in interpreting facial expressions of emotion including fear, exhibits an intact ability to express this and other basic emotions. This dissociation suggests that a single neural module does not support all aspects of the social communication of emotional state.

Amygdala↗

Atlas of the serotonin-containing cell bodies and fibers in the central nervous system of the hedgehog.

Immunocytochemistry with an antiserum raised against serotonin was used to provide detailed description of the serotonin (5-HT)-containing cell bodies and fibers in the CNS of the hedgehog (Erinaceus europeaus). The distribution of the 5-HT-positive cells and the pattern of 5-HT innervation resembled those described in other mammalian species but several differences were also noticed. The nine B groups of Dahlstrom and Fuxe (1964) were observed, except for the B 4 group which was not detected in the hedgehog. Neuron-like immunoreactive cells were also observed in brain regions located outside the brainstem reticular formation. Among the latter the olfactory tubercle and the thalamus have not been described to contain 5-HT cell bodies in other mammals. The number and the "lateralization" of 5-HT-positive neurons in areas outside the midline raphe were more limited than those described in the rodents and much more limited than in the carnivores and the primates. 5-HT-positive axons were unevenly distributed throughout the hedgehog's CNS. From all neocortical areas, which displayed the highest innervation density in the layer I, somatosensory and visual areas were the most heavily and lightly innervated ones respectively. Other regions of the forebrain exhibiting dense serotoninergic innervation were: olfactory cortex; olfactory tubercle; subiculum; lateral septal nucleus; stratum; medial and basal amygdaloid nuclei. Dense serotoninergic innervation were also found to receive the following brainstem structures: lateral hypothalamic area; dorsal part of the suprachiasmatic nucleus; arcuate nucleus; median eminence; habenular nuclei; centromedian thalamic nucleus; ventral tegmental area; medial part of the substantia nigra; interpeduncular nucleus; locus coeruleus; cuneiform nucleus; motor nucleus of the trigeminal nerve; facial nucleus; parabrachial nucleus; prepositus hypoglossi nucleus; medial subnucleus of the nucleus of the solitary tract; hypoglossal nucleus; dorsal motor nucleus of the vagus. In the spinal cord, laminae IX and X received the heaviest innervation.

Animals↗

Hyperinsulinemia in rats with obesity-inducing amygdaloid lesions.

Electrolytic lesions of the posterodorsal aspects of the medial division of the extended amygdala in female rats result in hyperphagia and excessive weight gain. In the present study, the effects of such lesions on plasma insulin, glucose, corticosterone, and adrenocorticotropic hormone were assessed during a period of food restriction and again after a 15-day period of food ad libitum. Compared with control animals, the rats with amygdaloid lesions were hyperinsulinemic under both conditions and gained substantially more weight when fed ad libitum. No difference between groups was observed for the other hormones. It is concluded that damage to the posterodorsal aspects of the medial amygdala results in a primary metabolic dysfunction that accounts, at least in part, for the overeating and excessive weight gain.

Amygdala↗

Distribution of NMDA and AMPA receptor subunits at thalamo-amygdaloid dendritic spines.

Synapses onto dendritic spines in the lateral amygdala formed by afferents from the auditory thalamus represent a site of plasticity in Pavlovian fear conditioning. Previous work has demonstrated that thalamic afferents synapse onto LA spines expressing glutamate receptor (GluR) subunits, but the GluR subunit distribution at the synapse and within the cytoplasm has not been characterized. Therefore, we performed a quantitative analysis for alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor subunits GluR2 and GluR3 and N-methyl-D-aspartate (NMDA) receptor subunits NR1 and NR2B by combining anterograde labeling of thalamo-amygdaloid afferents with postembedding immunoelectron microscopy for the GluRs in adult rats. A high percentage of thalamo-amygdaloid spines was immunoreactive for GluR2 (80%), GluR3 (83%), and NR1 (83%), while a smaller proportion of spines expressed NR2B (59%). To compare across the various subunits, the cytoplasmic to synaptic ratios of GluRs were measured within thalamo-amygdaloid spines. Analyses revealed that the cytoplasmic pool of GluR2 receptors was twice as large compared to the GluR3, NR1, and NR2B subunits. Our data also show that in the adult brain, the NR2B subunit is expressed in the majority of in thalamo-amygdaloid spines and that within these spines, the various GluRs are differentially distributed between synaptic and non-synaptic sites. The prevalence of the NR2B subunit in thalamo-amygdaloid spines provides morphological evidence supporting its role in the fear conditioning circuit while the differential distribution of the GluR subtypes may reflect distinct roles for their involvement in this circuitry and synaptic plasticity.

Amygdala↗

A peptidergic basis for sexual behavior in mammals.

Vasopressin (VP) is a peptide neurotransmitter in the limbic system of rats. It is synthesized in the medial amygdaloid nucleus in the presence of sex steroids, transported to other limbic structures such as the hippocampus and septum and secreted there by a calcium-dependent process. In the hippocampus, VP acts on cerebral microvessels and local circuit interneurons. Its excitatory action on the inhibitory interneurons produces near-total shutdown of electrical activity of the efferent fibers of pyramidal cells, the projection neurons of the hippocampus. Stimulation of the medial amygdala and release of the endogenous VP duplicates these effects and, since they are blocked by ventricular application of a VP antagonist, the effects are almost certainly mediated by endogenous VP. Recording from the VP-containing cell bodies or of the hippocampal action of the peptide indicates that the system is selectively involved with the early stages of sexual behavior, specifically those appetitive behaviors that anticipate coitus. Stimulation of the VP cells produces alterations in sexual behavior in a manner consistent with the hypothesis that the medial amygdala organizes the appetitive phase of recognition of an appropriate partner and sexual arousal. This role for the medial amygdala complements the proposed role of nearby structures in the consummatory, reward and learned aspects of sexual behavior. Association between VP, oxytocin (OT) and homologs with sexual behavior is very widespread among vertebrates, including amphibians, reptiles, primates and humans. Humans and other primates display a phenomenon called 'concealed ovulation' that may have played a role in the evolution of social structures. The review concludes with a discussion of possible experimental strategies for evaluating the possible role of VP in concealed ovulation and other conditions in which sexual behavior occurs outside of estrus.

Animals↗

Functional neuroimaging of normal human sleep by positron emission tomography.

Functional neuroimaging using positron emission tomography has recently yielded original data on the functional neuroanatomy of human sleep. This paper attempts to describe the possibilities and limitations of the technique and clarify its usefulness in sleep research. A short overview of the methods of acquisition and statistical analysis (statistical parametric mapping, SPM) is presented before the results of PET sleep studies are reviewed. The discussion attempts to integrate the functional neuroimaging data into the body of knowledge already acquired on sleep in animals and humans using various other techniques (intracellular recordings, in situ neurophysiology, lesional and pharmacological trials, scalp EEG recordings, behavioural or psychological description). The published PET data describe a very reproducible functional neuroanatomy in sleep. The core characteristics of this 'canonical' sleep may be summarized as follows. In slow-wave sleep, most deactivated areas are located in the dorsal pons and mesencephalon, cerebellum, thalami, basal ganglia, basal forebrain/hypothalamus, prefrontal cortex, anterior cingulate cortex, precuneus and in the mesial aspect of the temporal lobe. During rapid-eye movement sleep, significant activations were found in the pontine tegmentum, thalamic nuclei, limbic areas (amygdaloid complexes, hippocampal formation, anterior cingulate cortex) and in the posterior cortices (temporo-occipital areas). In contrast, the dorso-lateral prefrontal cortex, parietal cortex, as well as the posterior cingulate cortex and precuneus, were the least active brain regions. These preliminary studies open up a whole field in sleep research. More detailed explorations of sleep in humans are now accessible to experimental challenges using PET and other neuroimaging techniques. These new methods will contribute to a better understanding of sleep functions.

Animals↗

Region-specific expression of GABAA receptor alpha 3 and alpha 4 subunits mRNAs in the rat brain.

The expression of mRNAs encoding the alpha 3 and alpha 4 subunits of the gamma-aminobutyric acid A (GABAA) receptor in the rat brain was investigated by in situ hybridization histochemistry. Both subunits showed a wide but uneven distribution, which did not coincide with the distribution of any other subunit so far reported. The cerebral cortex, anterior olfactory nucleus, lateral septum, subiculum, lateral and medial nuclei of the amygdaloid complex, anterior nuclei of the thalamus, pars compacta of the substantia nigra, trigeminal sensory nuclei, and cochlear nucleus were some of the areas where strong expression of mRNA for both the alpha 3 and alpha 4 subunits was detected. In the mitral cell layer of the olfactory bulb, the preoptic area and locus coeruleus, strong expression of only the alpha 3 subunit was detected. In the granular cell layer of the olfactory bulb, caudate-putamen, tenia tecta, pyramidal cell layer of the CA region and granular cell layer of the dentate gyrus in the hippocampal formation, dorsomedial and ventrolateral nuclei of the thalamus, dorsal part of the lateral geniculate body, preolivary nuclei and pontine nuclei, only the alpha 4 subunit showed strong expression. The diverse distribution of these two subunits is considered to indicate that each has a different role in the central nervous system.

Animals↗

[Behavioral and EEG effects of Zingiber mioga Roscoe (water soluble fraction) (author's transl)].

Behavioral and EEG effects of water soluble fraction extracted from Zingiber mioga Roscoe (Z. mioga) were investigated in mice, rats and rabbits. Z. mioga was dissolved in isotonic saline and given i.p. into mice and rats, and i.v. into rabbits, respectively. Z. mioga at doses of 50 approximately 400 mg/kf produced a marked reduction in locomotor activity of mice in the open-field test. The peak time of reduction was 30 min after the injection. In mice, Z. mioga at the same doses lowered significantly the rectal temperature and prolonged the sleeping time induced by thiopental-Na (40 mg/kg, i.v.). Z. mioga at a dose of 400 mg/kg had no anticonvulsant effects and it produced a slight muscle relaxation in mice. Z. mioga at doses of 50 approximately 200 mg/kg induced a significant inhibition of the active conditioned avoidance response of the rat in a shuttle box without affecting the unconditioned escape response. In the step-down method, however, the passive conditioned avoidance response was rarely affected by Z. mioga, but the response was suppressed by chlorpromazine. In rabbits with chronically implanted electrodes, Z. mioga at doses of 20--30 mg/kg induced a drowsy pattern of spontaneous EEG, ilel high voltage slow waves in the neocortex and amygdala, and desynchronization in the case of hippocampal theta waves. The EEG arousal response to the external auditory stimulation was inhibited by the same doses of Z. mioga, whereas it failed to suppress the arousal response to either the midbrain reticular or posterior hypothalamic stimulation, as with chlorpromazine. Neither the recruiting response nor the photic driving response were affected by Z. mioga. On the other hand, the limbic after-discharges to the hippocampal or amygdaloid stimulation were enhanced by Z. mioga as well as chlorpromazin, but they were inhibited by diazepam. The EEG effects of Z. mioga were qualitatively similar to chlorpromazine, but not to diazepam. These results indicate the similarity of behavioral and EEG effects of Z. mioga to those seen with neuroleptics such as chlorpromazine.

Animals↗

The output of the hippocampus is inhibited during social behavior in the male rat.

During sexual behavior in the male rat, peptidergic cells in the medial amygdaloid nucleus become active and release a vasopressin-like peptide. The present experiments were designed to examine hippocampal changes as a result of this peptide's action during sexual behaviors. Chronic field-potential recordings from the hippocampus of male rats were acquired in a wide variety of social and nonsocial circumstances. Hippocampal responses that resemble the known action of the vasopressin-like peptide were seen only with social stimuli such as sexual stimuli and stimuli that led to aggressive behavior between males. The results show that the occasions of peptide action in the hippocampus correlate with the occasions of peptide release as determined by recording from the peptidergic cell bodies. The results are interpreted to indicate that the amygdala projection to the hippocampus has a special role to play in social behavior.

Animals↗

Ibotenic acid lesions in the amygdaloid central nucleus but not in the lateral subthalamic area prevent the acquisition of differential Pavlovian conditioning of bradycardia in rabbits.

The present study examined the effect of ibotenic acid lesions in the amygdaloid central nucleus (ACe) or in the lateral zona incerta of the subthalamus (LZI) on the acquisition of differential Pavlovian conditioning of bradycardia in rabbits. Previous work has shown that bilateral electrolytic lesions in either ACe or LZI abolished the retention of conditioned heart rate (HR) responses. In order to determine whether these findings were due to destruction of cells intrinsic to ACe or LZI, ibotenic acid lesions were placed bilaterally in either structure or in control sites. Following recovery, animals were subjected to differential Pavlovian conditioning in which one tone (CS+) was paired with periorbital shock and a second tone (CS-) was presented alone. It was found that destruction of cell bodies in ACe, but not LZI, prevented the acquisition of the differential bradycardiac conditioned response. In addition, ACe lesions did not interfere with baseline HR, the HR orienting response, the HR unconditioned response to shock, or the concomitantly conditioned corneoretinal potential. The results of this study suggest that destruction of cells intrinsic to ACe selectively prevents the acquisition of differentially conditioned HR, and perhaps other conditioned responses related to conditioned arousal, but does not affect unlearned HR responses or specific somatomotor conditioned responses.

Amygdala↗

GABAergic input to cholinergic forebrain neurons: an ultrastructural study using retrograde tracing of HRP and double immunolabeling.

Amygdalopetal cholinergic neurons in the ventral pallidum were identified by combining choline acetyltransferase (ChAT) immunohistochemistry with retrograde tracing of horseradish peroxidase (HRP) following injections of the tracer in the basolateral amygdaloid nucleus. Although ChAT-positive terminals were identified in the ventral pallidum, they were never seen in contact with either immunonegative or ChAT-positive amygdalopetal neurons. In material, in which immunostaining against glutamic acid decarboxylase (GAD), the synthesizing enzyme for GABA was combined with retrograde tracing of HRP from the basolateral amygdaloid nucleus, GAD-positive terminals were seen to contact immunonegative amygdalopetal neurons. In addition, when sections of the rostral forebrain were processed, first to preserve and identify the transported HRP, and then were sequentially tested for both ChAT and GAD immunohistochemistry with the immunoperoxidase reaction for both tissue antigens, GAD-immunopositive terminals were seen to make synaptic contacts with cholinergic amygdalopetal neurons. These results suggest that amygdalopetal, presumably cholinergic, neurons receive GAD-positive terminals. In separate experiments using immunoperoxidase for ChAT and ferritin-avidin for GAD labeling, we confirmed the presence of GAD-containing terminals on cholinergic neurons. In addition, cholinergic terminals were seen in synaptic contact with GAD-positive cell bodies. These morphological studies suggest that direct GABAergic-cholinergic and cholinergic-GABAergic interactions take place in the rostral forebrain.

Amygdala↗

Differences in basal levels of CREB and NPY in nucleus accumbens regions between C57BL/6 and DBA/2 mice differing in inborn alcohol drinking behavior.

An increasing body of evidence suggests that genetic factors play a role in alcohol drinking behaviors. C57BL/6J (C57) mice innately consume larger amounts of alcohol compared to that consumed by DBA/2J (DBA) mice. Furthermore, alterations in cAMP-responsive element binding (CREB) protein function in the brain have been implicated in alcohol drinking behaviors. The present investigation examined innate expression and phosphorylation of CREB in various brain structures of C57 and DBA mice. It was found that CREB expression and phosphorylation was lower, specifically in the shell structure of the nucleus accumbens, in C57 mice compared to that in DBA mice. CREB expression and phosphorylation were similar in other brain regions such as the nucleus accumbens core and the cortical, amygdaloid, hippocampal, and striatal structures of C57 and DBA mice. The expression of a cAMP-inducible gene, neuropeptide Y (NPY), was also investigated in the nucleus accumbens region of C57 and DBA mice. It was found that in C57 mice, NPY protein levels were lower in the shell but not in the core structure of the nucleus accumbens compared to that in DBA mice. It was also found that C57 mice are not innately anxious, but they consume larger amounts of alcohol than do DBA mice. Because the shell structure of the nucleus accumbens has been implicated in reward mechanisms of alcohol, it is possible that lower CREB function in this brain structure may be in part associated with the excessive alcohol drinking behavior of C57 mice.

Alcohol Drinking↗