Abstract
Identification of candidate risk genes and alteration in the expression of proteins involved in regulating inhibitory neuron function in various psychiatric disorders, support the notion that GABAergic neuron dysfunction plays an important role in disease etiology. Genetic variations in neuregulin and its receptor kinase ErbB4, expressed exclusively by GABAergic neurons in the CNS, have been linked with schizophrenia. In the amygdala, ErbB4 is highly expressed in GABAergic intercalated cell clusters (ITCs), which play a critical role in amygdala-dependent behaviors. It is however unknown whether ErbB4 deletion from ITCs affects their synaptic properties and function in amygdala circuitry. Here, we examined the impact of ErbB4 deletion on inhibitory and excitatory circuits recruiting medial paracapsular ITCs (mpITCs) using electrophysiological techniques. Ablation of ErbB4 in mpITCs suppressed NMDA receptor-mediated synaptic transmission at thalamo-mpITC synapses and enhanced thalamic driven GABAergic transmission onto mpITCs. Furthermore, long-term potentiation (LTP) at thalamo-mpITC synapses was compromised in ErbB4 mutant mice, indicating that ErbB4 activity is critical for LTP at these synapses. Together, our findings suggest that ErbB4 deletion from mpITCs disrupts excitation-inhibition balance and learning mechanisms in amygdala circuits.
Highlights
The amygdala plays a critical role in acquisition and storage of fear memory and other social-emotional-related behaviors (LeDoux, 2000, 2007; Felix-Ortiz and Tye, 2014; Felix-Ortiz et al, 2016)
The mean frequency of miniature inhibitory postsynaptic currents (mIPSCs) was similar in WT and ErbB4 conditional knockout (cKO) mice, mIPSC amplitudes were significantly enhanced in ErbB4 cKO mice (Figures 1H–J)
ErbB4 deletion selectively enhanced spontaneous and thalamic-driven inhibition onto medial paracapsular ITCs (mpITCs) resulting in an excitation-inhibition imbalance in ErbB4 cKO mice
Summary
The amygdala plays a critical role in acquisition and storage of fear memory and other social-emotional-related behaviors (LeDoux, 2000, 2007; Felix-Ortiz and Tye, 2014; Felix-Ortiz et al, 2016). The central nucleus of the amygdala (CeA) is striatum-like, with majority of GABAergic neurons. In addition to these nuclei is a network of interconnected GABAergic neurons organized in clusters surrounding the BLA known as the intercalated cell clusters (ITCs). These neurons express the dopamine D1 receptor (Drd1) (Fuxe et al, 2003; Palomares-Castillo et al, 2012) and are required for fear expression and
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