CRF Facilitates Calcium Release from Intracellular Stores in Midbrain Dopamine Neurons

Abstract

Changes in cytosolic calcium are crucial for numerous processes including neuronal plasticity. This study investigates the regulation of cytosolic calcium by corticotropin-releasing factor (CRF) in midbrain dopamine neurons. The results demonstrate that CRF stimulates the release of intracellular calcium from stores through activation of adenylyl cyclase and PKA. Imaging and photolysis experiments showed that the calcium originated from dendrites and required both functional IP3 and ryanodine receptor channels. The elevation in cytosolic calcium potentiated calcium-sensitive potassium channels (sK) activated by action potentials and metabotropic Gq-coupled receptors for glutamate and acetylcholine. This increase in cytosolic calcium activated by postsynaptic Gs-coupled CRF receptors may represent a fundamental mechanism by which stress peptides and hormones can shape Gq-coupled receptor-mediated regulation of neuronal excitability and synaptic plasticity in dopamine neurons.

A role for corticotropin-releasing factor signaling in the lateral habenula and its modulation by early-life stress

“…Intra-pipette GDPβS prevented CRF-induced increase in LHb intrinsic excitability (Figure 4C). Both intracellular release of Ca 2+ from internal stores and extracellular Ca 2+ influx have previously been shown to be involved in CRFR1 signaling in other brain areas (31, 32). To further investigate whether an increase in postsynaptic Ca 2+ signaling is involved downstream of CRFR1 activation, BAPTA (a fast Ca 2+ chelator) was used intracellularly through the patch pipette.…”

In Vivo Ethanol Experience Increases D2 Autoinhibition in the Ventral Tegmental Area

“…It should be noted that reduced dopamine release after ethanol withdrawal has been detected in both the core and shell of the NAc (Weiss et al, 1996). Although electrophysiological identification of dopamine neurons has been challenged (Margolis et al, 2006), the criteria described above have been used in recent studies performing recordings from the lateral part of the VTA in horizontal slices (Ahn et al, 2010;Beckstead et al, 2009;Ford et al, 2006;Riegel and Williams, 2008;Wanat et al, 2008;Zhang et al, 2010).…”

Functions and Modulation of Neuronal SK Channels

“…Interestingly, in midbrain dopaminergic neurons, activation of protein kinase A potentiates SK channel-mediated outward currents, via increased release of intracellular calcium [124]. This is in direct contrast to the direct actions of PKA on SK channels in the hippocampus and amygdala, which reduce SK channel function [82,83,148].…”

“…This activates SK channels, which mediate a slow inhibitory postsynaptic potential (IPSP), causing a transient pause in action potential discharge. The SK channel-mediated hyperpolarisation is also triggered in these neurons by calcium release from internal stores following muscarinic receptor activation [122], activation of a 1 adrenoceptors [123], and corticotrophinreleasing factor, via activation of protein kinase A [124]. Dendritic SK channels that are activated during repetitive firing have also been shown to control synaptic transmission in dopaminergic neurons of the ventral tegmental area by regulating endocannabinoid release [125].…”