Calcium-Permeable AMPA Receptors Promote Endocannabinoid Signaling at Parvalbumin Interneuron Synapses in the Nucleus Accumbens Core
Kevin M. Manz,
Dipanwita Ghose,
Brandon D. Turner,
Anne Taylor,
Jennifer Becker,
Carrie A. Grueter,
Brad A. Grueter
Affiliations
Kevin M. Manz
Medical Scientist Training Program, Vanderbilt University, Nashville, TN 37232, USA; Neuroscience Graduate Program, Vanderbilt University, Nashville, TN 37232, USA; Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Dipanwita Ghose
Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Brandon D. Turner
Neuroscience Graduate Program, Vanderbilt University, Nashville, TN 37232, USA
Anne Taylor
Neuroscience Graduate Program, Vanderbilt University, Nashville, TN 37232, USA
Jennifer Becker
Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Carrie A. Grueter
Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37232, USA; Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Brad A. Grueter
Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37232, USA; Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Center for Addiction Research, Vanderbilt University, Nashville, TN 37232, USA; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA; Corresponding author
Summary: Synaptic plasticity is a key mechanism of learning and memory. Synaptic plasticity mechanisms within the nucleus accumbens (NAc) mediate differential behavioral adaptations. Feedforward inhibition in the NAc occurs when glutamatergic afferents onto medium spiny neurons (MSNs) collateralize onto fast-spiking parvalbumin (PV)-expressing interneurons (PV-INs), which exert GABAergic control over MSN action potential generation. Here, we find that feedforward glutamatergic synapses onto PV-INs in the NAc core selectively express Ca2+-permeable AMPA receptors (CP-AMPARs). Ca2+ influx by CP-AMPARs on PV-INs triggers long-term depression (LTD) mediated by endocannabinoid (eCB) signaling at presynaptic cannabinoid type-1 (CB1) receptors (CB1Rs). Moreover, CP-AMPARs authorize tonic eCB signaling to negatively regulate glutamate release probability. Blockade of CP-AMPARs in the NAc core in vivo is sufficient to disinhibit locomotor output. These findings elucidate mechanisms by which PV-IN-embedded microcircuits in the NAc undergo activity-dependent shifts in synaptic strength.
