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Behavioural Brain Research Feb 2015Classical eyeblink conditioning (EBC), a simple form of associative learning, has long been served as a model for motor learning and modulation. The neural circuitry of... (Review)
Review
Classical eyeblink conditioning (EBC), a simple form of associative learning, has long been served as a model for motor learning and modulation. The neural circuitry of EBC has been studied in detail in rabbits. However, its underlying molecular mechanisms remain unclear. The advent of mouse transgenics has generated new perspectives on the studies of the neural substrates and molecular mechanisms essential for EBC. Results about EBC in mice differ in some aspects from those obtained in other mammals. Here, we review the current studies about the neural circuitry and molecular mechanisms underlying delay and trace EBC in mice. We conclude that brainstem-cerebellar circuit plays an essential role in DEC while the amygdala modulates this process, and that the medial prefrontal cortex (mPFC) as a candidate is involved in the extra-cerebellar mechanism underlying delay eyeblink conditioning (DEC) in mice. We propose the Amygdala-Cerebellum-Prefrontal Cortex-Dynamic-Conditioning Model (ACPDC model) for DEC in mice. As to trace eyeblink conditioning (TEC), the forebrain regions may play an essential role in it, whereas cerebellar cortex seems to be out of the neural circuitry in mice. Moreover, the molecular mechanisms underlying DEC and TEC in mice differ from each other. This review provides some new information and perspectives for further research on EBC.
Topics: Amygdala; Animals; Association Learning; Blinking; Cerebellum; Conditioning, Eyelid; Mice; Neural Pathways; Prefrontal Cortex; Prosencephalon; Reflex; Time Factors
PubMed: 25448430
DOI: 10.1016/j.bbr.2014.10.006 -
Alcohol (Fayetteville, N.Y.) Dec 2015
Topics: Alcoholism; Cerebral Cortex; Congresses as Topic; Genomics; Glucocorticoids; Humans; National Institute on Alcohol Abuse and Alcoholism (U.S.); Neostriatum; Neural Pathways; Prosencephalon; Stress Disorders, Post-Traumatic; Stress, Psychological; United States
PubMed: 26704671
DOI: 10.1016/j.alcohol.2015.11.007 -
Nature Reviews. Genetics Jan 2020
Topics: Genomics; Humans; Organoids; Prosencephalon
PubMed: 31641219
DOI: 10.1038/s41576-019-0189-0 -
FASEB Journal : Official Publication of... May 2021Adult neurogenesis occurs particularly in the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ) of the lateral ventricle. This continuous...
Adult neurogenesis occurs particularly in the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ) of the lateral ventricle. This continuous addition of neurons to pre-existing neuronal networks is essential for intact cognitive and olfactory functions, respectively. Purinergic signaling modulates adult neurogenesis, however, the role of individual purinergic receptor subtypes in this dynamic process and related cognitive performance is poorly understood. In this study, we analyzed the role of P2Y receptor in the neurogenic niches and in related forebrain functions such as spatial working memory and olfaction using mice with a targeted deletion of the P2Y receptor (P2Y2 ). Proliferation, migration, differentiation, and survival of neuronal precursor cells (NPCs) were analyzed by BrdU assay and immunohistochemistry; signal transduction pathway components were analyzed by immunoblot. In P2Y2 mice, proliferation of NPCs in the SGZ and the SVZ was reduced. However, migration, neuronal fate decision, and survival were not affected. Moreover, p-Akt expression was decreased in P2Y2 mice. P2Y2 mice showed an impaired performance in the Y-maze and a higher latency in the hidden food test. These data indicate that the P2Y receptor plays an important role in NPC proliferation as well as in hippocampus-dependent working memory and olfactory function.
Topics: Animals; Cell Movement; Cell Proliferation; Female; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurogenesis; Olfactory Bulb; Prosencephalon; Receptors, Purinergic P2Y2
PubMed: 33817825
DOI: 10.1096/fj.202002419RR -
Biochemical Pharmacology Jan 2018Drugs originate from the discovery of compounds, natural or synthetic, that bind to proteins (receptors, enzymes, transporters, etc.), the interaction of which modulates... (Review)
Review
Drugs originate from the discovery of compounds, natural or synthetic, that bind to proteins (receptors, enzymes, transporters, etc.), the interaction of which modulates biological cascades that have potential therapeutic benefit. Rational strategies for identifying novel drug therapies are typically based on knowledge of the structure of the target proteins and the design of new chemical entities that modulate these proteins in a beneficial manner. The present review discusses a novel approach to drug discovery based on the identification and characterization of auxiliary proteins, the transmembrane AMPA receptor regulatory proteins (TARPs) that are associated with AMPA receptors. Utilizing these auxiliary proteins in compound screening led to the discovery of the TARP-dependent-AMPA forebrain selective receptor antagonist (TDAA), LY3130481/CERC-611 that is currently in clinical development for epilepsy.
Topics: Animals; Benzothiazoles; Drug Discovery; Humans; Prosencephalon; Protein Subunits; Pyrazoles; Receptors, AMPA
PubMed: 28987594
DOI: 10.1016/j.bcp.2017.09.015 -
The Journal of Comparative Neurology Aug 2018Nonapeptide receptors, like oxytocin receptor (OTR) and vasopressin 1a receptor (V1aR), modulate a variety of functions across taxa, and mediate phenotypic variation...
Nonapeptide receptors, like oxytocin receptor (OTR) and vasopressin 1a receptor (V1aR), modulate a variety of functions across taxa, and mediate phenotypic variation within and between species. Despite the popularity of studying nonapeptides in adults, developmental perspectives on properties of OTR and V1aR expression are lacking. Study of prairie voles (Microtus ochrogaster) has facilitated an understanding of mechanisms of social behavior and provides great potential to inform how early life experiences alter phenotype. We provide the first comprehensive profiling of OTR and V1aR in male and female prairie voles across postnatal development and into adulthood. Differences in receptor densities across the forebrain were region- and sex-specific. Postnatal changes in receptor expression fell into four themes: (a) constant over time, (b) increasing with age, (c) decreasing with age, or (d) peaking during late pre-weaning (postnatal day 15-21). We also examined the influence of post-weaning social and spatial enrichment (i.e., environmental complexity) on OTR and V1aR. Environmental complexity appeared to promote expression of OTR in males and females, and reduced expression of V1aR across several brain regions in males. Our results show that nonapeptide receptor profiles are plastic over development and suggest that different patterns of expression might represent functional differences in sensitivity to nonapeptide activation over a period when social environments are dynamic. Our results on environmental complexity suggest that nonapeptide sensitivity responds flexibly to different environmental contexts during development. Understanding the developmental trajectories of nonapeptide receptors provides a better understanding of the dynamic nature of social behavior and the underlying mechanisms.
Topics: Aging; Animals; Arvicolinae; Environment; Female; Grassland; Housing, Animal; Male; Neuropeptides; Pair Bond; Prosencephalon; Receptors, Oxytocin; Receptors, Vasopressin; Sex Characteristics; Sexual Behavior, Animal
PubMed: 29665010
DOI: 10.1002/cne.24450 -
Annals of Clinical and Translational... Nov 2021Previous studies have demonstrated that infants are typically born with a left-greater-than-right forebrain asymmetry that reverses throughout the first year of life. We...
OBJECTIVES
Previous studies have demonstrated that infants are typically born with a left-greater-than-right forebrain asymmetry that reverses throughout the first year of life. We hypothesized that critically ill term-born and premature patients following surgical and critical care for long-gap esophageal atresia (LGEA) would exhibit alteration in expected forebrain asymmetry.
METHODS
Term-born (n = 13) and premature (n = 13) patients, and term-born controls (n = 23) <1 year corrected age underwent non-sedated research MRI following completion of LGEA treatment via Foker process. Structural T1- and T2-weighted images were collected, and ITK-SNAP was used for forebrain tissue segmentation and volume acquisition. Data were presented as absolute (cm ) and normalized (% total forebrain) volumes of the hemispheres. All measures were checked for normality, and group status was assessed using a general linear model with age at scan as a covariate.
RESULTS
Absolute volumes of both forebrain hemispheres were smaller in term-born and premature patients in comparison to controls (p < 0.001). Normalized hemispheric volume group differences were detected by T1-weighted analysis, with premature patients demonstrating right-greater-than-left hemisphere volumes in comparison to term-born patients and controls (p < 0.01). While normalized group differences were very subtle (a right hemispheric predominance of roughly 2% of forebrain volume), they represent a deviation from the expected pattern of hemispheric brain asymmetry.
INTERPRETATION
Our pilot quantitative MRI study of hemispheric volumes suggests that premature patients might be at risk of altered expected left-greater-than-right forebrain asymmetry following repair of LGEA. Future neurobehavioral studies in infants born with LGEA are needed to elucidate the functional significance of presented anatomical findings.
Topics: Esophageal Atresia; Female; Humans; Infant; Magnetic Resonance Imaging; Male; Pilot Projects; Prosencephalon
PubMed: 34662511
DOI: 10.1002/acn3.51465 -
Proceedings of the National Academy of... Nov 2022The craniote central nervous system has been divided into rostral, intermediate, and caudal sectors, with the rostral sector containing the vertebrate forebrain and...
The craniote central nervous system has been divided into rostral, intermediate, and caudal sectors, with the rostral sector containing the vertebrate forebrain and midbrain. Here, network science tools were used to create and analyze a rat hierarchical structure-function subsystem model of intrarostral sector neural connectivity between gray matter regions. The hierarchy has 109 bottom-level subsystems and three upper-level subsystems corresponding to voluntary behavior control, cognition, and affect; instinctive survival behaviors and homeostasis; and oculomotor control. As in previous work, subsystems identified based on their coclassification as network communities are revealed as functionally related. We carried out focal perturbations of neural structural connectivity comprehensively by computationally lesioning each region of the network, and the resulting effects on the network's modular (subsystem) organization were systematically mapped and measured. The pattern of changes was found to be correlated with three structural attributes of the lesioned region: region centrality (degree, strength, and betweenness), region position in the hierarchy, and subsystem distribution of region neural outputs and inputs. As expected, greater region centrality results, on average, in stronger lesion impact and more distributed lesion effects. In addition, our analysis suggests that strongly functionally related regions, belonging to the same bottom-level subsystem, exhibit similar effects after lesioning. These similarities account for coherent patterns of disturbances that align with subsystem boundaries and propagate through the network. These systematic lesion effects and their similarity across functionally related regions are of potential interest for theoretical, experimental, and clinical studies.
Topics: Animals; Rats; Prosencephalon; Cerebral Cortex; Mesencephalon
PubMed: 36322764
DOI: 10.1073/pnas.2210931119 -
Neurobiology of Aging Mar 2020We analyzed education, as a proxy of cognitive reserve, and the cholinergic pathway in Alzheimer's disease (AD), to test the hypothesis that education might modulate the...
We analyzed education, as a proxy of cognitive reserve, and the cholinergic pathway in Alzheimer's disease (AD), to test the hypothesis that education might modulate the relationship between clinical symptoms and metabolic and structural changes in AD. We included 84 subjects and compared between diagnostic groups and different educational levels the glucose metabolism of basal forebrain (BFM) and volume of the basal forebrain, the major cholinergic structure, and hippocampus (HM) (and hippocampal volume), a relevant projection site for the basal forebrain. Correlations with the global cognitive status and education in the whole sample were also performed. Patients with AD dementia showed reduced basal forebrain volume, hippocampal volume, and HM compared with controls. In the whole group, the global cognitive status was positively correlated with BFM and HM. Among high-educated subjects, mild cognitive impairment showed higher BFM and HM in comparison to other diagnostic groups. Our results suggest that in mild cognitive impairment subjects with a higher educational level, cholinergic activity is upregulated and this appears to have a compensatory effect, which may be lost in later symptomatic stages.
Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cognitive Dysfunction; Cognitive Reserve; Educational Status; Female; Glucose; Hippocampus; Humans; Male; Organ Size; Prosencephalon
PubMed: 32008856
DOI: 10.1016/j.neurobiolaging.2019.11.013 -
Current Biology : CB Nov 2023Bluehead wrasses (Thalassoma bifasciatum) follow a socially controlled mechanism of sex determination. A socially dominant initial-phase (IP) female is able to transform...
Bluehead wrasses (Thalassoma bifasciatum) follow a socially controlled mechanism of sex determination. A socially dominant initial-phase (IP) female is able to transform into a new terminal-phase (TP) male if the resident TP male is no longer present. TP males display an elaborate array of courtship behaviors, including both color changes and motor behaviors. Little is known concerning the neural circuits that control male-typical courtship behaviors. This study used glutamate iontophoresis to identify regions that may be involved in courtship. Stimulation of the following brain regions elicited diverse types of color change responses, many of which appear similar to courtship color changes: the ventral telencephalon (supracommissural nucleus of the ventral telencephalon [Vs], lateral nucleus of the ventral telencephalon [Vl], ventral nucleus of the ventral telencephalon [Vv], and dorsal nucleus of the ventral telencephalon [Vd]), parts of the preoptic area (NPOmg and NPOpc), entopeduncular nucleus, habenular nucleus, and pretectal nuclei (PSi and PSm). Stimulation of two regions in the posterior thalamus (central posterior thalamic [CP] and dorsal posterior thalamic [DP]) caused movements of the pectoral fins that are similar to courtship fluttering and vibrations. Furthermore, these responses were elicited in female IP fish, indicating that circuits for sexual behaviors typical of TP males exist in females. Immunohistochemistry results revealed regions that are more active in fish that are not courting: interpeduncular nucleus, red nucleus, and ventrolateral thalamus (VL). Taken together, we propose that the telencephalic-habenular-interpeduncular pathway plays an important role in controlling and regulating courtship behaviors in TP males; in this model, in response to telencephalic input, the habenular nucleus inhibits the interpeduncular nucleus, thereby dis-inhibiting forebrain regions and promoting the expression of courtship behaviors.
Topics: Animals; Female; Male; Courtship; Telencephalon; Prosencephalon; Thalamus; Perciformes; Fishes
PubMed: 37898122
DOI: 10.1016/j.cub.2023.10.003