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bioRxiv · 10.1101/2024.10.08.617188

Cholecystokinin-expressing GABA neurons elicit long-term potentiation in the cortical inhibitory synapses and attenuate sound-shock associative memory

Zhang, G.·Pang, K. K.·Chen, X.·Huang, F.·He, J.
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Abstract

Neuronal interactions between inhibitory and excitatory neurons play a pivotal role in regulating the balance of excitation and inhibition in the central nervous system (CNS). Consequently, the efficacy of inhibitory/excitatory synapses profoundly affects neural network processing and overall neuronal functions. Here, we describe a novel form of long-term potentiation (LTP) induced at cortical inhibitory synapses and its behavioral consequences. We show that high-frequency laser stimulation (HFLS) of GABAergic neurons elicit inhibitory LTP (i-LTP) in pyramidal neurons of the auditory cortex (AC). The selective activation of cholecystokinin-expressing GABA (GABACCK) neurons is essential for the formation of HFLS-induced i-LTP, rather than the classical parvalbumin (PV) neurons and somatostatin (SST) neurons. Intriguingly, i-LTP can be evoked in the AC by adding the exogenous neuropeptide CCK when PV neurons and SST neurons are selectively activated in PV-Cre and SST-Cre mice, respectively. Additionally, we discovered that low-frequency laser stimulation (LFLS) of PV neurons paired with HFLS of GABACCK neurons potentiates the inhibitory effect of PV interneurons on pyramidal neurons, thereby generating heterosynaptic i-LTP in the AC. Notably, light activation of GABACCK neurons in CCK-Cre mice significantly attenuates sound-shock associative memory, while stimulation of PV neurons does not affect this memory in PV-Cre mice. In conclusion, these results demonstrate a critical mechanism regulating the excitation-inhibition balance and modulating learning and memory in cortical circuits. This mechanism might serve as a potential target for the treatment of neurological disorders, including epilepsy and Alzheimers disease.

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Zhang, G., Pang, K. K., Chen, X., Huang, F., He, J.. 2024-10-08. Cholecystokinin-expressing GABA neurons elicit long-term potentiation in the cortical inhibitory synapses and attenuate sound-shock associative memory. https://doi.org/10.1101/2024.10.08.617188

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