Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was conducted to examine the excitability changes induced in cerebral cortical neurons during prolonged microstimulation with a spatially dense microelectrodes array. The arrays of 16 iridium microelectrodes were implanted chronically into the postcruciate gyrus of cats. Neuronal responses characteristic of single pyramidal tract axons (ULRs) were recorded in the medullary pyramid. 7 h of pulsing of individual electrodes at 50 Hz and at 4 nC/ph induced little or no change in the ULRs' electrical thresholds. The thresholds also were quite stable when 4 of the 16 microelectrodes were pulsed on each of 14 consecutive days. However, when all 16 microelectrodes were pulsed for 7 h at 4 nC/ph, the threshold of approximately half of the ULRs became elevated. Recovery of excitability required 2-18 days. Prolonged sequential (interleaved) pulsing of the 16 microelectrodes induced less depression of excitability than did simultaneous pulsing, but only when the stimulus amplitude was low (12 A, 1.8 nC/ph). Stimulation at a higher amplitude (15 nC/ph) induced much more depression of excitability. These findings imply that multiple processes mediate the stimulation-induced depression of neuronal excitability. The data also demonstrate that the depression can be reduced by employing a stimulus regimen in which the inherent spatial resolution of the array is maximized (sequential pulsing at an amplitude in which there is minimal overlap of the effective current fields).
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PMID:The effects of prolonged intracortical microstimulation on the excitability of pyramidal tract neurons in the cat. 1187 34

Both retrospective and prospective clinical studies have demonstrated positive associations of smoking with psychiatric disorders such as schizophrenia, depression and anxiety. Neuronal nicotinic acetylcholine receptors (nAChR) belong to a family of ligand-gated ion channels that are widely distributed in the brain. The pre-synaptically located nAChR, which are composed of alpha3 or alpha4 subunits in combination with beta2 subunit on axon terminals, modulate the multiple transmission release. Several studies indicated which individual nicotinic receptor subtype is responsible for mediating each of the behavioral effects of nicotine. A reduced number of alpha7 nicotinic receptor subtypes in the hippocampus were reported in schizophrenic patients. In addition, it was assumed that nicotine provided useful therapeutic treatment for a variety of cognitive impairments including those found in Alzheimer's disease, schizophrenia and attention deficit hyperactive disorder. Both alpha7 and alpha4beta2 nicotinic receptors in the hippocampus are involved in these phenomena. In the genetic depressive rats, nicotine showed antidepressant-like effects in forced swim models of depression, suggesting the involvement of alpha4beta2 nicotinic receptor in this phenomenon. Thus, it appears likely that pre-synaptic nAChR on monoaminergic fibers are composed of alpha3 or alpha4 subunits in combination with the beta2 subunit, and these subunit compositions mediate dopaminergic and noradrenergic release, and glutamate is mainly controlled by the alpha7 subunit. All these findings suggest that nicotine and other nicotinic drugs warrant further study for possible clinical prescription to psychiatric disorders.
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PMID:Neuronal nicotinic receptor and psychiatric disorders: functional and behavioral effects of nicotine. 1192 12

Neuronal adaptation to repetitive sensory stimuli is ubiquitous in the mammalian cortex. Despite its prevalence, the cellular mechanisms underlying this basic physiological property remain a matter of dispute. In this issue of Neuron, Chung et al. provide conclusive evidence that depression of thalamocortical synapses may play a significant role in the expression of neuronal adaptation in the rat somatosensory cortex.
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PMID:Depression at thalamocortical synapses: the key for cortical neuronal adaptation? 1198 74

Neuronal nicotinic acetylcholine receptors (nAChR) are a family of ligand-gated ion channels that have a pentameric structure composed of five membrane spanning subunits. Recent progress in clinical and neurochemical studies have shown that neuronal nAChR are involved in some psychiatric disorders such as schizophrenia, depression, and anxiety via its stimulating effect of multiple neurotransmitters. It has been suggested that the high prevalence of smoking in the patients with psychiatric disorders is an attempt to alleviate some psychiatric symptoms using the central stimulatory effect of nicotine (a self-medication effort) or to alleviate the exacerbated symptoms by nicotine withdrawal. Moreover, recent studies with mutant mice lacking specific nAChR subunits and animal models of psychiatric disorders have indicated the psychopharmacological role of individual nAChR subunits in psychiatric disorders. Thus, it is suggested that alpha 7 nAChR is involved in the attention deficit of schizophrenic patients and that alpha 4 beta 2 nAChR is related to nicotine dependence or the withdrawal symptoms.
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PMID:[Involvement of neuronal nicotinic receptor in psychiatric disorders]. 1206 Nov 41

We propose a neural network model of the inferior colliculus (IC) for human echolocation. Neuronal mechanisms for human echolocation were investigated by simulating the model. The model consists of the neural networks of the central nucleus (ICc) and external nucleus (ICx) of the inferior colliculus. The neurons of the ICc receive interaural sound stimuli via multiple contralateral delay lines and a single ipsilateral delay line. The neurons of the ICc send output signals to the neurons of the ICx in a convergent manner. We stimulated the ICc with pairs of a direct sound (a sonar sound) and an echo sound (the reflection from an object). Information about the distance between the model and the object is expressed by the delay time of the echo sound with respect to the direct sound. The results presented here show that neurons of the ICc responsive to interaural onset time differences contribute to the creation of an auditory distance map in the ICx. We trained the model with various pairs of direct-echo sounds and modified synaptic connection strengths of the networks according to the Hebbian rule. It is shown that self-organized long-term depression of lateral inhibitory synaptic connections plays an important role in enhancing echolocation skills.
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PMID:A neural network model of the inferior colliculus with modifiable lateral inhibitory synapses for human echolocation. 1206 88

In addition to regulating the neuroendocrine stress response, corticotropin-releasing hormone (CRH) has been implicated in both normal and pathological behavioral and cognitive responses to stress. CRH-expressing cells and their target neurons possessing CRH receptors (CRF1 and CRF2) are distributed throughout the limbic system, but little is known about the regulation of limbic CRH receptor function and expression, including regulation by the peptide itself. Because CRH is released from limbic neuronal terminals during stress, this regulation might play a crucial role in the mechanisms by which stress contributes to human neuropsychiatric conditions such as depression or posttraumatic stress disorder. Therefore, these studies tested the hypothesis that CRH binding to CRF1 influenced the levels and mRNA expression of this receptor in stress-associated limbic regions of immature rat. Binding capacities and mRNA levels of both CRF1 and CRF2 were determined at several time points after central CRH administration. CRH downregulated CRF1 binding in frontal cortex significantly by 4 h. This transient reduction (no longer evident at 8 h) was associated with rapid increase of CRF1 mRNA expression, persisting for >8 h. Enhanced CRF1 expression-with a different time course-occurred also in hippocampal CA3, but not in CA1 or amygdala, CRF2 binding and mRNA levels were not altered by CRH administration. To address the mechanisms by which CRH regulated CRF1, the specific contributions of ligand-receptor interactions and of the CRH-induced neuronal stimulation were examined. Neuronal excitation without occupation of CRF1 induced by kainic acid, resulted in no change of CRF1 binding capacity, and in modest induction of CRF1 mRNA expression. Furthermore, blocking the neuroexcitant effects of CRH (using pentobarbital) abolished the alterations in CRF1 binding and expression. These results indicate that CRF1 regulation involves both occupancy of this receptor by its ligand, as well as "downstream" cellular activation and suggest that stress-induced perturbation of CRH-CRF1 signaling may contribute to abnormal neuronal communication after some stressful situations.
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PMID:Corticotropin-releasing hormone (CRH) downregulates the function of its receptor (CRF1) and induces CRF1 expression in hippocampal and cortical regions of the immature rat brain. 1209 84

IP3 is an important second messenger to release Ca2+ from internal store. IP3receptor (IP3R) works as an IP3 induced Ca2+ release channel and requires IP3 and Ca2+ as coagoinist. We found IP3R is involved in fertilization, meiosis and mitosis by using a specific antibody. We further found that IICR is essential for determination of dorsoventral axis formation. Neuronal type 1 IP3R-deficient mice generated by a gene-targeting technique exhibit a significant reduction of birth rate and abnormal behavior (ataxia and seizure). Long-term depression of the cerebellum was blocked in the type 1 IP3R-deficient mice. Long-term potentiation (LTP) of CA1 hippocampus was enhanced but depotentiation and LTP suppression was reduced in IP3R1-deficient mice. These evidences suggest that IICR is involved in neuronal plasticity. The coupling mechanism between ER Ca2+ stores and plasma membrane store-operated channels is crucial to Ca2+ signaling. Recently we found that IP3R interacts with the TRP3 Ca2+ channel on the plasma membrane and functional coupling of IP3R to TRP3 channel is important for store operated Ca2+ entry. Recently we found that IP3R is involved in determination of polarity and input specificity of activity-induced synaptic modification.
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PMID:[IP3 receptor, a Ca2+ oscilator--role of IP3 receptor in development and neural plasticity]. 1249 67

Neuronal Ca(2+) sensor protein-1 (NCS-1) is a member of the Ca(2+) binding protein family, with three functional Ca(2+) binding EF-hands and an N-terminal myristoylation site. NCS-1 is expressed in brain and heart during embryonic and postnatal development. In neurons, NCS-1 facilitates neurotransmitter release, but both inhibition and facilitation of the Ca(2+) current amplitude have been reported. In heart, NCS-1 co-immunoprecipitates with K(+) channels and modulates their activity, but the potential effects of NCS-1 on cardiac Ca(2+) channels have not been investigated. To directly assess the effect of NCS-1 on the various types of Ca(2+) channels we have co-expressed NCS-1 in Xenopus oocytes, with Ca(V)1.2, Ca(V)2.1, and Ca(V)2.2 Ca(2+) channels, using various subunit combinations. The major effect of NCS-1 was to decrease Ca(2+) current amplitude, recorded with the three different types of alpha(1) subunit. When expressed with Ca(V)2.1, the depression of Ca(2+) current amplitude induced by NCS-1 was dependent upon the identity of the beta subunit expressed, with no block recorded without beta subunit or with the beta(3) subunit. Current-voltage and inactivation curves were also slightly modified and displayed a different specificity toward the beta subunits. Taken together, these data suggest that NCS-1 is able to modulate cardiac and neuronal voltage-gated Ca(2+) channels in a beta subunit specific manner.
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PMID:Down-regulation of voltage-gated Ca2+ channels by neuronal calcium sensor-1 is beta subunit-specific. 1249 89

Neuronal heterotopia has a strong association with epilepsy, but the mechanisms that underlie this relationship are largely unknown. We have utilized the in utero irradiated rat model to study circuit abnormalities in experimentally induced subcortical heterotopic gray matter. Spontaneous and miniature inhibitory (IPSCs) and excitatory (EPSCs) postsynaptic currents were recorded from visualized heterotopic pyramidal neurons in in vitro hemispheric slices and compared with control neocortical pyramidal neurons using the whole cell patch-clamp technique. The frequency of spontaneous and miniature IPSCs was significantly reduced in pyramidal neurons from heterotopic cortex. Amplitude and kinetics of IPSCs were not different between the two groups. Spontaneous and miniature EPSCs were not different between the two groups. Short-term synaptic plasticity of stimulus-evoked EPSCs showed depression in heterotopic neurons and facilitation in control pyramidal neurons. This study shows a selective impairment of the GABAergic circuitry in experimental heterotopic gray matter. We have reported similar findings in normotopic dysplastic cortex from this model. Taken together, these studies demonstrate a pervasive defect in inhibition throughout the cortex of irradiated rats with cortical dysplasia and neuronal heterotopia. This may have important implications regarding cortical development and function following in utero injuries.
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PMID:Reduction of spontaneous inhibitory synaptic activity in experimental heterotopic gray matter. 1252 67

Neuronal excitability and long-term synaptic plasticity at excitatory synapses are critically dependent on the level of inhibition, and accordingly, changes of inhibitory synaptic efficacy should have great impact on neuronal function and neural network processing. We describe here a form of activity-dependent long-term depression at hippocampal inhibitory synapses that is triggered postsynaptically via glutamate receptor activation but is expressed presynaptically. That is, glutamate released by repetitive activation of Schaffer collaterals activates group I metabotropic glutamate receptors at CA1 pyramidal cells, triggering a persistent reduction of GABA release that is mediated by endocannabinoids. This heterosynaptic form of plasticity is involved in changes of pyramidal cell excitability associated with long-term potentiation at excitatory synapses and could account for the effects of cannabinoids on learning and memory.
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PMID:Heterosynaptic LTD of hippocampal GABAergic synapses: a novel role of endocannabinoids in regulating excitability. 1274 83


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