title: Inhibition of presynaptic calcium transients in cortical inputs to the dorsolateral striatum by metabotropic GABA(B) and mGlu2/3 receptors.
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 GABA(B) 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 (Ca(2+) ) indicator GCaMP6 to assess presynaptic Ca(2+) in corticostriatal projections to the DLS. Using simultaneous photometric presynaptic Ca(2+) and striatal field potential recordings, we report that relative to P/Q-type Ca(2+) channels, N-type channels preferentially contributed to evoked presynaptic Ca(2+) influx in motor cortex projections to, and excitatory transmission in, the DLS. Activation of GABA(B) or mGlu2/3 receptors inhibited both evoked presynaptic Ca(2+) transients and striatal field potentials. mGlu2/3 receptor-mediated depression did not require functional N-type Ca(2+) 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.
authors.affiliation: Section on Synaptic Pharmacology & In Vivo Neural Function, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, US National Institutes of Health, Rockville, MD, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Kupferschmidt
authors.affiliation: Section on Synaptic Pharmacology & In Vivo Neural Function, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, US National Institutes of Health, Rockville, MD, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Lovinger
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D002540:Cerebral Cortex / Q000502:physiology*; D013181:Cortical Spreading Depression / Q000502:physiology; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D023421:Models, Animal; D009433:Neural Inhibition / Q000502:physiology; D010783:Photometry; D017729:Presynaptic Terminals / Q000502:physiology*; D018080:Receptors, GABA-B / Q000502:physiology*; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D015220:Calcium Channels; D018080:Receptors, GABA-B; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3