Search results for "GABA"
showing 10 items of 390 documents
Haploinsufficiency of Tsc2 Leads to Hyperexcitability of Medial Prefrontal Cortex via Weakening of Tonic GABAB Receptor-mediated Inhibition.
2020
Abstract Loss-of-function mutation in one of the tumor suppressor genes TSC1 or TSC2 is associated with several neurological and psychiatric diseases, including autism spectrum disorders (ASDs). As an imbalance between excitatory and inhibitory neurotransmission, E/I ratio is believed to contribute to the development of these disorders, we investigated synaptic transmission during the first postnatal month using the Tsc2+/− mouse model. Electrophysiological recordings were performed in acute brain slices of medial prefrontal cortex. E/I ratio at postnatal day (P) 15–19 is increased in Tsc2+/− mice as compared with wildtype (WT). At P25–30, facilitated GABAergic transmission reduces E/I rati…
A systematic comparison of kinetic modelling methods generating parametric maps for [11C]-(R)-PK11195
2006
[(11)C]-(R)-PK11195 is presently the most widely used radiotracer for the monitoring of microglia activity in the central nervous system (CNS). Microglia, the resident immune cells of the brain, play a critical role in acute and chronic diseases of the central nervous system and in host defence against neoplasia. The purpose of this investigation was to evaluate the reliability and sensitivity of five kinetic modelling methods for the formation of parametric maps from dynamic [(11)C]-(R)-PK11195 studies. The methods we tested were the simplified reference tissue model (SRTM), basis pursuit, a simple target-to-reference ratio, the Logan plot and a wavelet based Logan plot. For the reliabilit…
Nrg1 haploinsufficiency alters inhibitory cortical circuits
2021
Neuregulin 1 (NRG1) and its receptor ERBB4 are schizophrenia (SZ) risk genes that control the development of both excitatory and inhibitory cortical circuits. Most studies focused on the characterization ErbB4 deficient mice. However, ErbB4 deletion concurrently perturbs the signaling of Nrg1 and Neuregulin 3 (Nrg3), another ligand expressed in the cortex. In addition, NRG1 polymorphisms linked to SZ locate mainly in non-coding regions and they may partially reduce Nrg1 expression. Here, to study the relevance of Nrg1 partial loss-of-function in cortical circuits we characterized a recently developed haploinsufficient mouse model of Nrg1 (Nrg1tm1Lex). These mice display SZ-like behavioral d…
Identification of a gene overexpressed in aphids reared under short photoperiod.
2003
Most aphids develop a cyclic parthenogenesis life-cycle. After several generations of viviparously produced parthenogenetic females, follows a single annual generation of sexual individuals, usually in autumn, that mate and lay the sexual eggs. Shortening of photoperiod at the end of the summer (together with temperature) is a key factor inducing the sexual response. Currently no genes involved in the cascade of events that lead to the appearance of sexual forms have been reported. After a Differential Display RT-PCR survey performed on Acyrthosiphon pisum aphids, we identified a gene that is overexpressed in aphids reared under short photoperiod conditions that induce sexuality in this spe…
An update to Hippocampome.org by integrating single-cell phenotypes with circuit function in vivo.
2021
Understanding brain operation demands linking basic behavioral traits to cell-type specific dynamics of different brain-wide subcircuits. This requires a system to classify the basic operational modes of neurons and circuits. Single-cell phenotyping of firing behavior during ongoing oscillations in vivo has provided a large body of evidence on entorhinal–hippocampal function, but data are dispersed and diverse. Here, we mined literature to search for information regarding the phase-timing dynamics of over 100 hippocampal/entorhinal neuron types defined in Hippocampome.org. We identified missing and unresolved pieces of knowledge (e.g., the preferred theta phase for a specific neuron type) a…
Coincident glutamatergic depolarizations enhance GABAA receptor-dependent Cl- influx in mature and suppress Cl- efflux in immature neurons.
2021
The impact of GABAergic transmission on neuronal excitability depends on the Cl--gradient across membranes. However, the Cl--fluxes through GABAA receptors alter the intracellular Cl- concentration ([Cl-]i) and in turn attenuate GABAergic responses, a process termed ionic plasticity. Recently it has been shown that coincident glutamatergic inputs significantly affect ionic plasticity. Yet how the [Cl-]i changes depend on the properties of glutamatergic inputs and their spatiotemporal relation to GABAergic stimuli is unknown. To investigate this issue, we used compartmental biophysical models of Cl- dynamics simulating either a simple ball-and-stick topology or a reconstructed CA3 neuron. Th…
Vascular Third Nerve Compression—A Possible Cause of Episodic Vertical Diplopia?
2006
We report a 74-year-old man with a 2-year history of episodes of vertical diplopia. In the beginning, there was one episode every 2–3 months, which increased over time to an average of one episode every 2 weeks. These complaints were attributed to an MRI-documented vascular third nerve compression. Treatment with gabapentin (400 mg q.i.d.) was followed by cessation of episodic diplopia.
Nitric oxide and brain hyperexcitability.
2004
Nitric oxide (NO) is a gaseous messenger involved in atypical forms of intercellular communications, able to exert a strong functional modulation of several neurotransmitter systems. In particular, NO heavily influences the excitatory neurotransmitter glutamate, mainly through NMDA receptors, and the inhibitory neurotransmitter GABA, mainly through GABA A receptors. Due to the involvement of glutamate and GABA in a delicate balance conditioning the functional status of the neural cells, this interaction suggests a role for NO in regulating neuronal excitability and its transition towards hyperexcitability phenomena. This article reviews the main knowledge about the relationships existing be…
Functional Integration of Neuronal Precursors in the Adult Murine Piriform Cortex
2018
Abstract The extent of functional maturation and integration of nonproliferative neuronal precursors, becoming neurons in the adult murine piriform cortex, is largely unexplored. We thus questioned whether precursors eventually become equivalent to neighboring principal neurons or whether they represent a novel functional network element. Adult brain neuronal precursors and immature neurons (complex cells) were labeled in transgenic mice (DCX-DsRed and DCX-CreERT2 /flox-EGFP), and their cell fate was characterized with patch clamp experiments and morphometric analysis of axon initial segments. Young (DCX+) complex cells in the piriform cortex of 2- to 4-month-old mice received sparse synapt…
Preclinical evidence of new opioid modulators for the treatment of addiction.
2010
Addiction to opiates is one of the most severe forms of substance dependence, and despite a variety of pharmacological approaches to treat it, relapse is observed in a high percentage of subjects. New pharmacological compounds are necessary to improve the outcome of treatments and reduce adverse side effects. Moreover, drugs that act on the opioid system can also be of benefit in the treatment of alcohol or cocaine addiction. AREA COVERED BY THIS REVIEW: Recent preclinical studies of pharmacological agents for the treatment of opiate addiction (2008 to the present date).The reader will be informed of the latest drugs shown in animal models to modify dependence on opiates and the reinforcing…