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- Title
Inhibition of presynaptic calcium transients in cortical inputs to the dorsolateral striatum by metabotropic GABA<sub>B</sub> and mGlu2/3 receptors.
- Authors
Kupferschmidt, David A.; Lovinger, David M.
- Abstract
Key points Plastic changes at cortical inputs to the dorsolateral striatum (DLS) underlie skill learning and habit formation, so characterizing the mechanisms by which these inputs are regulated is important for understanding the neural basis of action control., We developed a novel approach using the genetically encoded calcium (Ca2+) indicator GCaMP6 and brain slice photometry to assess evoked presynaptic Ca2+ transients in cortical inputs to the DLS and study their regulation by GABAB and mGlu2/3 receptors., GABAB and mGlu2/3 receptor activation caused clear reductions in electrical stimulus-evoked presynaptic Ca2+ transients in corticostriatal inputs to the DLS., Functional P/Q-type voltage-gated Ca2+ channels were required for the normal inhibitory action of corticostriatal mGlu2/3 receptors., We provide direct evidence of presynaptic Ca2+ inhibition by G protein-coupled receptors at corticostriatal projections., Abstract Cortical inputs to the dorsolateral striatum (DLS) are dynamically regulated during skill learning and habit formation, and are dysregulated in disorders characterized by impaired action control. Therefore, a mechanistic investigation of the processes regulating corticostriatal transmission is key to understanding DLS-associated circuit function, behaviour and pathology. Presynaptic GABAB and group II metabotropic glutamate (mGlu2/3) receptors exert marked inhibitory control over corticostriatal glutamate release in the DLS, yet the signalling pathways through which they do so are unclear. We developed a novel approach using the genetically encoded calcium (Ca2+) indicator GCaMP6 to assess presynaptic Ca2+ in corticostriatal projections to the DLS. Using simultaneous photometric presynaptic Ca2+ and striatal field potential recordings, we report that relative to P/Q-type Ca2+ channels, N-type channels preferentially contributed to evoked presynaptic Ca2+ influx in motor cortex projections to, and excitatory transmission in, the DLS. Activation of GABAB or mGlu2/3 receptors inhibited both evoked presynaptic Ca2+ transients and striatal field potentials. mGlu2/3 receptor-mediated depression did not require functional N-type Ca2+ channels, but was attenuated by blockade of P/Q-type channels. These findings reveal presynaptic mechanisms of inhibitory modulation of corticostriatal function that probably contribute to the selection and shaping of behavioural repertoires.
- Subjects
BRAIN physiology; SYNAPSES; GANGLIA; HABIT formation; NEURONS
- Publication
Journal of Physiology, 2015, Vol 593, Issue 10, p2295
- ISSN
0022-3751
- Publication type
Article
- DOI
10.1113/JP270045