Nicotine Exposure during Adolescence Leads to Changes of Synaptic Plasticity and Intrinsic Excitability of Mice Insular Pyramidal Cells at Later Life.

Hiroki Toyoda,Kohei Koga

doi:10.3390/ijms23010034

Abstract

To find satisfactory treatment for nicotine addiction, synaptic and cellular mechanisms should be investigated comprehensively. Synaptic transmission, plasticity and intrinsic excitability in various brain regions are known to be altered by acute nicotine exposure. However, it has not been addressed whether and how nicotine exposure during adolescence alters these synaptic events and intrinsic excitability in the insular cortex in adulthood. To address this question, we performed whole-cell patch-clamp recordings to examine the effects of adolescent nicotine exposure on synaptic transmission, plasticity and intrinsic excitability in layer V pyramidal neurons (PNs) of the mice insular cortex five weeks after the treatment. We found that excitatory synaptic transmission and potentiation were enhanced in these neurons. Following adolescent nicotine exposure, insular layer V PNs displayed enhanced intrinsic excitability, which was reflected in changes in relationship between current strength and spike number, inter-spike interval, spike current threshold and refractory period. In addition, spike-timing precision evaluated by standard deviation of spike timing was decreased following nicotine exposure. Our data indicate that adolescent nicotine exposure enhances synaptic transmission, plasticity and intrinsic excitability in layer V PNs of the mice insular cortex at later life, which might contribute to severe nicotine dependence in adulthood.

Highlights

Effective treatment of nicotine dependence is crucial for decreasing the severe morbidity and mortality in relation with tobacco smoking
Our data indicate that adolescent nicotine exposure enhances synaptic transmission, plasticity and intrinsic excitability in layer V pyramidal neurons (PNs) of the mice insular cortex at later life, which might contribute to severe nicotine dependence in adulthood
The present study demonstrated that nicotine exposure during adolescence enhanced synaptic transmission, plasticity and intrinsic excitability in layer V PNs of the mice insular cortex at later life

Summary

Introduction

Effective treatment of nicotine dependence is crucial for decreasing the severe morbidity and mortality in relation with tobacco smoking. Many efforts have been made to elucidate the synaptic and cellular mechanisms for nicotine addiction in rodents, there are currently still few effective treatments [1]. Adolescence is a sensitive period for drug consumption and addiction both in animals and humans [2,3] At this stage in life, a critical phase of the neurodevelopmental process, abuse of drugs including tobacco smoking can induce brain plasticity such as long-lasting changes in neural circuitry both in animals and humans [4,5,6]. Little study has been conducted regarding the effects of adolescent nicotine exposure on synaptic and cellular functions at later life in other rodent brain regions associated with nicotine addiction

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Results

Conclusion