Synapsin I Controls Synaptic Maturation of Long-Range Projections in the Lateral Amygdala in a Targeted Selective Fashion.

Eleonora Lugarà,Yann Humeau,Fabio Benfenati,Antonio De Fusco,Gabriele Lignani

doi:10.3389/fncel.2019.00220

Abstract

The amygdala, and more precisely its lateral nucleus, is thought to attribute emotional valence to external stimuli by generating long-term plasticity changes at long-range projections to principal cells. Aversive experience has also been shown to modify pre- and post-synaptic markers in the amygdala, suggesting their possible role in the structural organization of adult amygdala networks. Here, we focused on how the maturation of cortical and thalamic long-range projections occurs on principal neurons and interneurons in the lateral amygdala (LA). We performed dual electrophysiological recordings of identified cells in juvenile and adult GAD67-GFP mice after independent stimulation of cortical and thalamic afferent systems. The results demonstrate that synaptic strengthening occurs during development at synapses projecting to LA principal neurons, but not interneurons. As synaptic strengthening underlies fear conditioning which depends, in turn, on presence and increasing expression of synapsin I, we tested if synapsin I contributes to synaptic strengthening during development. Interestingly, the physiological synaptic strengthening of cortical and thalamic synapses projecting to LA principal neurons was virtually abolished in synapsin I knockout mice, but not differences were observed in the excitatory projections to interneurons. Immunohistochemistry analysis showed that the presence of synapsin I is restricted to excitatory contacts projecting to principal neurons in LA of adult mice. These results indicate that synapsin I is a key regulator of the maturation of synaptic connectivity in this brain region and that is expression is dependent on postsynaptic identity.

Highlights

Emotions, fear and anxiety are mostly encoded in the cerebral formation of the amygdala both in humans and rodents (LeDoux, 2003)
Target-Specific Synaptic Maturation Occurs at Long-Range Projections to the Lateral Amygdala During Postnatal Development
In order to characterize how and to what extent longrange projections contacted lateral amygdala (LA) over age, we compared the amount of excitatory current received simultaneously by principal neurons (PNs) and INs in 2–3 weeks and 3–6 months old WT/GAD67 mice while stimulating the external capsule or the internal capsule projections (Humeau et al, 2005; Figures 1A,B)

Summary

Introduction

Fear and anxiety are mostly encoded in the cerebral formation of the amygdala both in humans and rodents (LeDoux, 2003). Within the first postnatal week the LA cellular components undergo important developmental changes in circuit organization and physiological maturation of single cells (Berdel et al, 1997; Erlich et al, 2012; Ryan et al, 2016) so that, by the second postnatal week, the connections of the external capsule and the internal capsule within the LA neurons are fully established (Bouwmeester et al, 2002) According to this maturation profile, the mechanisms behind fear conditioning evolve from the youth to the adult stage (Pattwell et al, 2012, 2016; Shoji et al, 2016). Deletion of Syns impacts on multiple forms of synaptic plasticity in both vertebrate and invertebrate preparations (for a review, see Cesca et al, 2010) and, consistently, behavioral experiments have shown that fear conditioning, emotional memory and cognition fear responses are influenced by the expression of Syns (Corradi et al, 2008; Porton et al, 2010)

Methods

Results

Discussion

Conclusion