Goethe University, Institute of Neurophysiology, Neuroscience Center, Frankfurt am Main, Germany.
Published: June 2022
AI Article Synopsis
Article Abstract
The low-threshold L-type calcium channel Ca1.3 accelerates the pacemaker rate in the heart, but its functional role for the extended dynamic range of neuronal firing is still unresolved. Here, we show that Ca1.3 calcium channels act as unexpectedly simple, full-range linear amplifiers of firing rates for lateral dopamine substantia nigra (DA SN) neurons in mice. This means that they boost in vitro or in vivo firing frequencies between 2 and 50 hertz by about 30%. Furthermore, we demonstrate that clinically relevant, low nanomolar concentrations of the L-type channel inhibitor isradipine selectively reduce the in vivo firing activity of these nigrostriatal DA SN neurons at therapeutic plasma concentrations. Thus, our study identifies the pacemaker function of neuronal Ca1.3 channels and provides direct evidence that repurposing dihydropyridines such as isradipine is feasible to selectively modulate the in vivo activity of highly vulnerable DA SN subpopulations in Parkinson's disease.
The hippocampus is the brain's center for episodic memories. Its subregions, the dentate gyrus and CA1-3, are differentially involved in memory encoding and recall. Hippocampal principal cells represent episodic features like movement, space, and context, but less is known about GABAergic interneurons.
The dentate gyrus (DG) output plays a key role in the emergence of spatial and contextual map representation within the hippocampus during learning. Differences in neuronal network activity have been observed between left and right CA1-3 areas, implying lateralization in spatial coding properties. Whether bilateral differences of DG granule cell (GC) assemblies encoding spatial and contextual information exist remains largely unexplored.
Liaoning Provincial Key Laboratory of Cerebral Diseases, Department of Physiology, Dalian Medical University, Dalian, 116044, People's Republic of China.
G protein-coupled receptor 50 (GPR50) belongs to the G protein-coupled receptor which is highly homologous with the sequence of melatonin receptor MT1 and MT2. GPR50 expression has previously been reported in many brain regions, like cortex, midbrain, pons, amygdala. But, the distribution of GPR50 in the hippocampus and cortex and the cell types expressing GPR50 is not yet clear.
Decreased gamma-aminobutyric acid (GABA)-ergic neurons in the brain of both schizophrenic patients and animal models indicates that impairment of GABAergic function is implicated in pathophysiology of the disorder. Decreased GABAergic neurotransmission might be also involved in cognitive impairment, which is developed in schizophrenia. Brahmi () could be a new treatment and prevention for this cognitive deficit in schizophrenia by increasing GABAergic neurons to a normal level.
Transient ischemia in the whole brain leads to neuronal loss/death in vulnerable brain regions. The striatum, neocortex and hippocampus selectively loose specific neurons after transient ischemia. Just 5 minutes of transient ischemia can cause pyramidal neuronal death in the hippocampal cornu ammonis (CA) 1 field at 4 days after transient ischemia.
