Neuronal localization of the 5-HT2 receptor family in the amygdaloid complex

The amygdaloid complex (or amygdala), a heterogeneous structure located in the medial portion of the temporal lobe, is composed of deep, superficial, and “remaining” nuclei. This structure is involved in the generation of emotional behavior, in the formation of emotional memories and in the modulation of the consolidation of explicit memories for emotionally arousing events. The serotoninergic fibers originating in the dorsal and medial raphe nuclei are critically involved in amygdalar functions. Serotonin (5-hydroxytryptamine, 5-HT) regulates amygdalar activity through the activation of the 5-HT2 receptor family, which includes three receptor subtypes: 5-HT2A, 5-HT2B, and 5-HT2C. The distribution and the functional activity of the 5-HT2 receptor family has been studied more extensively than that of the 5-HT2A receptor subtypes, especially in the deep nuclei. In these nuclei, the 5-HT2A receptor is expressed on both pyramidal and non-pyramidal neurons, and could play a critical role in the formation of emotional memories. However, the exact role of the 5-HT2A receptor subtypes, as well as that of the 5-HT2B and 5-HT2C receptor subtypes, in the modulation of the amygdalar microcircuits requires additional study. The present review reports data concerning the distribution and the functional roles of the 5-HT2 receptor family in the amygdal

Functional anatomy of 5-HT2A receptors in the amygdala and hippocampal complex : relevance to memory functions

The amygdaloid complex and hippocampal region contribute to emotional activities, learning, and memory. Mounting evidence suggests a primary role for serotonin (5-HT) in the physiological basis of memory and its pathogenesis by modulating directly the activity of these two areas and their cross-talk. Indeed, both the amygdala and the hippocampus receive remarkably dense serotoninergic inputs from the dorsal and median raphe nuclei. Anatomical, behavioral and electrophysiological evidence indicates the 5-HT2A receptor as one of the principal postsynaptic targets mediating 5-HT effects. In fact, the 5-HT2A receptor is the most abundant 5-HT receptor expressed in these brain structures and is expressed on both amygdalar and hippocampal pyramidal glutamatergic neurons as well as on γ-aminobutyric acid (GABA)-containing interneurons. 5-HT2A receptors on GABAergic interneurons stimulate GABA release, and thereby have an important role in regulating network activity and neural oscillations in the amygdala and hippocampal region. This review will focus on the distribution and physiological functions of the 5-HT2A receptor in the amygdala and hippocampal region. Taken together the results discussed here suggest that 5-HT2A receptor may be a potential therapeutic target for those disorders related to hippocampal and amygdala dysfunction.peer-reviewe

Developmental changes of GABA immunoreactivity in cortico-thalamic networks of an absence seizure model

Absence seizures (ASs) are associated with abnormalities in gamma-aminobutyric acid (GABA) neurotransmission in the thalamus and the cortex. In the present study, we used light microscopy GABA immunocytochemistry to quantify the GABA-immunoreactive (GABA-IR) neurons and neuropil in the thalamic ventral basal (VB) nucleus, the nucleus reticularis thalami (NRT), the dorsal lateral geniculate (dLGN), the primary motor cortex (M1) and perioral region of the somatosensory cortex (S1po) of genetic absence epilepsy rats from Strasbourg (GAERS). We used both the relative non-epileptic control (NEC) and normal Wistar rats as control strains, and investigated GABA immunostaining at postnatal day 15 (P15), P25, and P90. The main findings were i) an increase in GABA-IR neuropil in the VB at P25 and P90 in GAERS but not in NEC and Wistar rats; ii) an increase in NRT GABA-IR neurons in GAERS and NEC, but not Wistar, rats at both P25 and P90; and iii) an increase in GABA-IR neuron density in S1po of GAERS at P25 and P90 and in Wistar at P90. These results indicate that the increased GABAergic innervation in the VB at P25 most likely contributes to the enhanced tonic inhibition observed in GAERS prior to AS onset, whereas the lack of any anatomo-morphological GABAergic differences in GAERS S1po suggests that functional more than structural abnormalities underlie the origin of cortical paroxysms in S1po of this AS model

Locus coeruleus complex of the family Delphinidae

The locus coeruleus (LC) is the largest catecholaminergic nucleus and extensively projects to widespread areas of the brain and spinal cord. The LC is the largest source of noradrenaline in the brain. To date, the only examined Delphinidae species for the LC has been a bottlenose dolphin (Tursiops truncatus). In our experimental series including different Delphinidae species, the LC was composed of five subdivisions: A6d, A6v, A7, A5, and A4. The examined animals had the A4 subdivision, which had not been previously described in the only Delphinidae in which this nucleus was investigated. Moreover, the neurons had a large amount of neuromelanin in the interior of their perikarya, making this nucleus highly similar to that of humans and non-human primates. This report also presents the first description of neuromelanin in the cetaceans' LC complex, as well as in the cetaceans' brain

Role for serotonin2A (5-HT2A) and 2C (5-HT2C) receptors in experimental absence seizures

Absence seizures (ASs) are the hallmark of childhood/juvenile absence epilepsy. Monotherapy with first-line anti-absence drugs only controls ASs in 50% of patients, indicating the need for novel therapeutic targets. Since serotonin family-2 receptors (5-HT2Rs) are known to modulate neuronal activity in the cortico-thalamo-cortical loop, the main network involved in AS generation, we investigated the effect of selective 5-HT2AR and 5-HT2CR ligands on ASs in the Genetic Absence Epilepsy Rats from Strasbourg (GAERS), a well established polygenic rat model of these non-convulsive seizures. GAERS rats were implanted with fronto-parietal EEG electrodes under general anesthesia, and their ASs were later recorded under freely moving conditions before and after intraperitoneal administration of various 5-HT2AR and 5-HT2CR ligands. The 5-HT2A agonist TCB-2 dose-dependently decreased the total time spent in ASs, an effect that was blocked by the selective 5-HT2A antagonist MDL11,939. Both MDL11,939 and another selective 5-HT2A antagonist (M100,907) increased the length of individual seizures when injected alone. The 5-HT2C agonists lorcaserin and CP-809,101 dose-dependently suppressed ASs, an effect blocked by the selective 5-HT2C antagonist SB 242984. In summary, 5-HT2ARs and 5-HT2CRs negatively control the expression of experimental ASs, indicating that selective agonists at these 5-HT2R subtypes might be potential novel anti-absence drugs

Preferential modulation of the lateral habenula activity by serotonin-2A rather than -2C receptors: Electrophysiological and neuroanatomical evidence

Aims: Serotonergic (5-HT) modulation of the lateral habenula (LHb) activity is central in normal and pathologic conditions such as mood disorders. Among the multiple 5-HT receptors (5-HTRs) involved, the 5-HT2CR seems to play a pivotal role. Yet, the role of 5-HT2ARs in the control of the LHb neuronal activity is completely unknown. Methods: Single-cell extracellular recording of the LHb neurons was used in rats to study the effect of the general activation and blockade of the 5-HT2CR and 5-HT2AR with Ro 60-0175 and SB242084, TCB-2 and MDL11939, respectively. The expression of both receptors in the LHb was confirmed using immunohistochemistry. Results: Cumulative doses (5-640 \uce\ubcg/kg, iv) of Ro 60-0175 and TCB-2 affected the activity of 34% and 63% of the LHb recorded neurons, respectively. LHb neurons were either inhibited at low doses or excited at higher doses of the 5-HT2A/CR agonists. SB242084 or MDL11939 (both at 200 \uce\ubcg/kg, iv) did not modify neuronal firing when injected alone, but reverted the bidirectional effects of Ro 60-0175 or TCB-2, respectively. 5-HT2CRs and 5-HT2ARs are expressed in less than the 20% of the LHb neurons, and they neither colocalize nor make heterodimers. Strikingly, only 5-HT2ARs are expressed by the majority of LHb astrocyte cells. Conclusions: Peripheral administration of 5-HT2AR agonist promotes a heterogeneous pattern of neuronal responses in the LHb, and these effects are more prominent than those induced by the 5-HT2CR activation

studies on tursiops truncatus and stenella coeruleoalba dolphin species from retinal cell morphological comparisons towards its surrounding environment

AbstractIn this current study, the retinal cell morphology of two dolphin species, Tursiops truncatus and Stenella coeruleoalba was compared, and supplemented with a miniature review of how it relates to surrounding environment. Retinal cell morphology involved sectioning and retino-separation of eyes, morphometric analysis of retinal cell layers and its corresponding neurons, followed by stratigraphy of both retina and area/density of ganglion neuron cell bodies. A qualification criteria was developed to describe both thickness and visibility. To relate with surrounding environment of studied species, we searched relevant synthesized literature combining such key words as 'dolphin', 'Tursiops truncatus', 'Stenella coeruleoalba', 'eye', 'vision', 'ecology' and 'environment'. Retinal cell morphology comparisons showed that the thickness of outer nuclear layer had upper (37.8 – 38.5 μm) whereas outer plexiform layer had lower (7.8 – 8.7 μm) range values, with some differences between individual retinal layers (p<0.05) but specific to some cases. Area of ganglion cell layer of multipolar neurons of retina of both studied species could surpass the 800 μm2 mark, which suggests the presence of 'giant' size cell types. Plausibly, the retino-morphological comparisons of studied dolphin species depict the context of micro-view, and able to relate with a macro-view with respect to its surrounding environment

Distribution of α-transducin and α-gustducin immunoreactive cells in the chicken (Gallus domesticus) gastrointestinal tract

The expression and distribution patterns of the taste signaling molecules, α-gustducin (Gαgust) and α-transducin (Gαtran) G-protein subunits, were studied in the gastrointestinal tract of the chicken (Gallus domesticus) using the immunohistochemical method. Gαgust and Gαtran immunoreactive (-IR) cells were observed in the mucosal layer of all examined segments, except the esophagus, crop, and the saccus cranialis of the gizzard. The highest numbers of Gαgust and Gαtran-IR cells were found in the proventriculus glands and along the villi of the pyloric, duodenum, and rectal mucosa. Gαgust and Gαtran-IR cells located in the villi of the jejunum, ileum, and cloaca were much less numerous, while only a few Gαgust and Gαtran-IR cells were detected in the mucosa of the proventriculus and cecum. In the crypts, IR cells were observed in the small and large intestine as well as in the cloaca. Gαgust and Gαtran-IR cells displayed elongated ("bottle-" or "pear-like") or rounded shape. The demonstration of Gαgust and Gαtran expression provides evidence for taste receptor mediated mucosal chemosensitivity in the chicken gastrointestinal tract

The laminar organization of the motor cortex in monodactylous mammals: a comparative assessment based on horse, chimpanzee, and macaque

The architecture of the neocortex classically consists of six layers, based on cytological criteria and on the layout of intra/interlaminar connections. Yet, the comparison of cortical cytoarchitectonic features across different species proves overwhelmingly difficult, due to the lack of a reliable model to analyze the connection patterns of neuronal ensembles forming the different layers. We first defined a set of suitable morphometric cell features, obtained in digitized Nissl-stained sections of the motor cortex of the horse, chimpanzee, and crab-eating macaque. We then modeled them using a quite general non-parametric data representation model, showing that the assessment of neuronal cell complexity (i.e., how a given cell differs from its neighbors) can be performed using a suitable measure of statistical dispersion such as the mean absolute deviation\u2014mean absolute deviation (MAD). Along with the non-parametric combination and permutation methodology, application of MAD allowed not only to estimate, but also to compare and rank the motor cortical complexity across different species. As to the instances presented in this paper, we show that the pyramidal layers of the motor cortex of the horse are far more irregular than those of primates. This feature could be related to the different organizations of the motor system in monodactylous mammals

Histochemical Analysis of Herniated Disc Tissue Surgically Removed from 27 Dogs

Hernias of intervertebral discs are a common canine disease that is usually treated surgically. Recently, a histological scoring system for surgically removed canine intervertebral herniated discs has been developed by scoring the lesions of both the anulus fibrosus (AF) and the nucleus pulposus (NP). Since the proportion of AF and NP in the surgical samples may vary, depending on the surgical approach, the aim of this study is to grade separately the lesions in AF and NP and to modify the previously described scoring system adding three parameters: inflammation, mineralization and neovascularization. Possible association of the modified grading system with clinical parameters were statistically assessed. Herniated disc material was collected from 27 dogs. AF was present in 10/27 cases and was classified as grade 2 in 4 cases, grade 3 in 5 cases and grade 4 in 1 case. The NP was present in all 27 cases and was classified as grade 2 in 1 case, grade 3 in 5 cases, grade 4 in 9 cases and grade 5 in 12 cases. A statistically significant association was evidenced between short pre-operative period and higher grade of both the NP and of the AF (P<0.01). Separating the grades of the AF and NP can be useful for a fair assessment of degeneration, and circumventing the limitation of the qualitative and quantitative variability of samples