Calcium-Permeable AMPA Receptors Promote Endocannabinoid Signaling at Parvalbumin Interneuron Synapses in the Nucleus Accumbens Core

Autor: Kevin M. Manz, Dipanwita Ghose, Anne Taylor, Brad A. Grueter, Carrie A. Grueter, Brandon D. Turner, Jennifer C. Becker
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
CB1 receptor
Interneuron
Action Potentials
Glutamic Acid
AMPA receptor
Nucleus accumbens
Medium spiny neuron
Synaptic Transmission
General Biochemistry
Genetics and Molecular Biology
Nucleus Accumbens
Article
03 medical and health sciences
Glutamatergic
Mice
0302 clinical medicine
Interneurons
medicine
Animals
Receptors
AMPA
lcsh:QH301-705.5
Neurons
Neuronal Plasticity
biology
Chemistry
musculoskeletal
neural
and ocular physiology
Long-Term Synaptic Depression
Endocannabinoid system
Mice
Inbred C57BL
CP-AMPA receptors
030104 developmental biology
medicine.anatomical_structure
Parvalbumins
lcsh:Biology (General)
nervous system
plasticity
Synaptic plasticity
Synapses
biology.protein
Calcium
feedforward inhibition
Neuroscience
Receptors
Calcium-Sensing
030217 neurology & neurosurgery
Parvalbumin
Endocannabinoids
Signal Transduction
Zdroj: Cell reports
Cell Reports, Vol 32, Iss 4, Pp 107971-(2020)
ISSN: 2211-1247
Popis: 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.
Graphical Abstract
In Brief Manz et al. show that CP-AMPARs are expressed at glutamatergic synapses onto PV-INs but not D1- or D2-expressing MSNs in the NAc core. Ca2+ influx through CP-AMPARs triggers endocannabinoid-dependent tone and synaptic plasticity. Intra-NAc blockade of CP-AMPARs in vivo increases basal locomotion.
Databáze: OpenAIRE
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