Noradrenergic Signaling Disengages Feedforward Transmission in the Nucleus Accumbens Shell
Autor: | Brad A. Grueter, Kevin M. Manz, Carrie A. Grueter, Brenda C Shields, Benjamin C. Coleman, Michael R. Tadross |
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Rok vydání: | 2021 |
Předmět: |
Male
0301 basic medicine Patch-Clamp Techniques Interneuron Optogenetics Nucleus accumbens Medium spiny neuron Inhibitory postsynaptic potential Synaptic Transmission Nucleus Accumbens Mice Norepinephrine 03 medical and health sciences Glutamatergic 0302 clinical medicine Interneurons Parasympathetic Nervous System Receptors Adrenergic alpha-2 Monoaminergic medicine Animals Research Articles Neurons Chemistry General Neuroscience Neural Inhibition Electrophysiological Phenomena Parvalbumins 030104 developmental biology Monoamine neurotransmitter medicine.anatomical_structure nervous system Female Nerve Net Neuroscience 030217 neurology & neurosurgery Signal Transduction |
Zdroj: | J Neurosci |
ISSN: | 1529-2401 0270-6474 |
Popis: | The nucleus accumbens shell (NAcSh) receives extensive monoaminergic input from multiple midbrain structures. However, little is known how norepinephrine (NE) modulates NAc circuit dynamics. Using a dynamic electrophysiological approach with optogenetics, pharmacology, and drugs acutely restricted by tethering (DART), we explored microcircuit-specific neuromodulatory mechanisms recruited by NE signaling in the NAcSh of parvalbumin (PV)-specific reporter mice. Surprisingly, NE had little direct effect on modulation of synaptic input at medium spiny projection neurons (MSNs). In contrast, we report that NE transmission selectively modulates glutamatergic synapses onto PV-expressing fast-spiking interneurons (PV-INs) by recruiting postsynaptically-localized α2-adrenergic receptors (ARs). The synaptic effects of α2-AR activity decrease PV-IN-dependent feedforward inhibition onto MSNs evoked via optogenetic stimulation of cortical afferents to the NAcSh. These findings provide insight into a new circuit motif in which NE has a privileged line of communication to tune feedforward inhibition in the NAcSh.SIGNIFICANCE STATEMENTThe nucleus accumbens (NAc) directs reward-related motivational output by integrating glutamatergic input with diverse neuromodulatory input from monoamine centers. The present study reveals a synapse-specific regulatory mechanism recruited by norepinephrine (NE) signaling within parvalbumin-expressing interneuron (PV-IN) feedforward inhibitory microcircuits. PV-IN-mediated feedforward inhibition in the NAc is instrumental in coordinating NAc output by synchronizing the activity of medium spiny projection neurons (MSNs). By negatively regulating glutamatergic transmission onto PV-INs via α2-adrenergic receptors (ARs), NE diminishes feedforward inhibition onto MSNs to promote NAc output. These findings elucidate previously unknown microcircuit mechanisms recruited by the historically overlooked NE system in the NAc. |
Databáze: | OpenAIRE |
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