Cholecystokinin-expressing GABA neurons elicit long-term potentiation in the cortical inhibitory synapses and attenuate sound-shock associative memory
Year: 2025
Type: article
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 (GABA CCK ) 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 GABA CCK neurons potentiates the inhibitory effect of PV interneurons on pyramidal neurons, thereby generating heterosynaptic i-LTP in the AC. Notably, light activation of GABA CCK 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 Alzheimer’s disease.
Source: Scientific Reports
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,690
Awards: G1383580875, Cholecystokinin receptor agonists as potential new drugs for rescuing learning and memory deficiency in aged wild type and Alzheimer’s Disease animals, CCK-B receptor antagonist for the treatment of depression in the mouse model, Platform Development for New Anti-epileptic Drug Evaluation and Pre-clinical Study of New Cholecystokinin Antagonists as New Anti-epileptic Drugs
OpenAlex ID: W4413525382