Disinhibition-assisted long-term potentiation in the prefrontal-amygdala pathway via suppression of somatostatin-expressing interneurons.

Wataru Ito,Brendon Fusco,Alexei Morozov

doi:10.1117/1.nph.7.1.015007

Abstract

.Significance: Natural brain adaptations often involve changes in synaptic strength. The artificial manipulations can help investigate the role of synaptic strength in a specific brain circuit not only in various physiological phenomena like correlated neuronal firing and oscillations but also in behaviors. High- and low-frequency stimulation at presynaptic sites has been used widely to induce long-term potentiation (LTP) and depression. This approach is effective in many brain areas but not in the basolateral amygdala (BLA) because the robust local GABAergic tone inside BLA restricts synaptic plasticity.Aim: We aimed at identifying the subclass of GABAergic neurons that gate LTP in the BLA afferents from the dorsomedial prefrontal cortex (dmPFC).Approach: Chemogenetic or optogenetic suppression of specific GABAergic neurons in BLA was combined with high-frequency stimulation of the BLA afferents as a method for LTP induction.Results: Chemogenetic suppression of somatostatin-positive interneurons (Sst-INs) enabled the ex vivo LTP by high-frequency stimulation of the afferent but the suppression of parvalbumin-positive interneurons (PV-INs) did not. Moreover, optogenetic suppression of Sst-INs with Arch also enabled LTP of the dmPFC-BLA synapses, both ex vivo and in vivo.Conclusions: These findings reveal that Sst-INs but not PV-INs gate LTP in the dmPFC-BLA pathway and provide a method for artificial synaptic facilitation in BLA.

Highlights

Optogenetics and chemogenetics have become the key methods for testing the causal role of specific neuronal populations and synapses in brain activities and animal behaviors
Optogenetic suppression of somatostatin-positive interneurons (Sst-INs) with Arch enabled long-term potentiation (LTP) of the dorsomedial prefrontal cortex (dmPFC)-basolateral amygdala (BLA) synapses, both ex vivo and in vivo. These findings reveal that Sst-INs but not parvalbuminpositive interneurons (PV-INs) gate LTP in the dmPFC-BLA pathway and provide a method for artificial synaptic facilitation in BLA
To obtain the mice-expressing hM4Di27 in Sst-INs or PV-INs, homozygous R26-LSL-GiDREADD males (JAX Stock No: 026219) on C57BL/6N background were crossed with homozygous interneuron-specific Cre driver females on 129SvEv background—either the Sst-IN-specific Cre driver (Sst-Cre), Ssttm2.1ðcreÞZjh[28] (JAX: 013044) or the PV-IN-specific Cre driver (PV-Cre), Pvalbtm1ðcreÞArbr[29] (JAX: 008069)

Summary

Introduction

Optogenetics and chemogenetics have become the key methods for testing the causal role of specific neuronal populations and synapses in brain activities and animal behaviors. The techniques employ depolarizing or hyperpolarizing neuronal compartments, like the soma, dendrites, and synaptic terminals, to trigger or suppress action potentials (APs) and release of neurotransmitters.[1,2] natural neuronal adaptations driven by experience and learning, or observed during development or in disease, involve brain alterations, in neuronal activity and in synaptic efficacy. The 20 Hz and theta-burst stimulation produced long-term potentiation (LTP) in the recurrent synapses of the hippocampal area CA34 and corticostriatal synapses,[5] respectively. The low-frequency stimulation produced long-term depression (LTD) in the inputs to the nucleus accumbens and basolateral amygdala (BLA) from the infralimbic cortex.[6,7] not all synapses follow the frequency rule. The high-frequency stimulation generated LTD in inputs from the BLA to the dorsomedial prefrontal cortex (dmPFC)[8] and failed to produce LTP in the prefrontal-amygdala synapses.[9]

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