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

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 parvalbuminpositive 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.

Downregulation of kainate receptors regulating GABAergic transmission in amygdala after early life stress is associated with anxiety-like behavior in rodents

“…SOM+ interneurons are also a critical part of the amygdala anxiety circuit, and changes in their excitability influence anxiety-like behaviors (reviewed by Prager et al [ 35 ], Babaev et al [ 37 ], Robinson and Thiele [ 57 ]). Dendritic inhibition via SOM+ interneurons efficiently gate generation of dendritic Ca+ signals and plasticity induction [ 58 – 60 ]. Therefore, the increase in SOM-mediated dendritic inhibition as an indirect consequence of lost GluK1 KAR function could contribute to the altered threshold for plasticity in LA, observed after early life stress [ 1 ].…”

Interneuron Types and Their Circuits in the Basolateral Amygdala

“…Indeed, recently it has been demonstrated that the spiking of amygdalar principal neurons evoked by synaptic excitation could be suppressed by activation of SST inhibitory cells (Wolff et al, 2014 ). This activation can even lead to gating long-term potentiation, at least at excitatory synapses of prefrontal-basal amygdala afferents (Ito et al, 2020 ).…”

Acetylcholine engages distinct amygdala microcircuits to gate internal theta rhythm

“…In the BLA, SOM INs have been implicated in modulating external inputs 45 , plasticity 69 , and feedforward 70 and feedback inhibition 71 . Here, we describe a novel role of SOM INs in gating activity of CCK INs to modulate BLA network synchronization.…”