Distinct neuronal excitability alterations of medial prefrontal cortex in early-life neglect model of rats

Abstract

Object: Early-life neglect has irreversible emotional effects on the central nervous system. In this work, we aimed to elucidate distinct functional neural changes in medial prefrontal cortex (mPFC) of model rats.

Methods: Maternal separation with early weaning was used as a rat model of early-life neglect. The excitation of glutamatergic and GABAergic neurons in rat mPFC was recorded and analyzed by whole-cell patch clamp.

Results: Glutamatergic and GABAergic neurons of mPFC were distinguished by typical electrophysiological properties. The excitation of mPFC glutamatergic neurons was significantly increased in male groups, while the excitation of mPFC GABAergic neurons was significant in both female and male groups, but mainly in terms of rest membrane potential and amplitude, respectively.

Conclusions: Glutamatergic and GABAergic neurons in medial prefrontal cortex showed different excitability changes in a rat model of early-life neglect, which can contribute to distinct mechanisms for emotional and cognitive manifestations.

Keywords: GABAergic; early-life neglect model; glutamatergic; maternal separation with early weaning; medial prefrontal cortex; neuronal excitability.

FIGURE 1

Electrophysiological properties of putative glutamatergic and GABAergic neurons in medial prefrontal cortex. (A) Schematic coronal section of a rat brain, showing the medial prefrontal cortex (mPFC). Recording electrodes were placed in layer II/III of mPFC. Excitation of neurons were recorded by whole‐cell patch clamp. (B–D) Summary histograms demonstrating different electrophysiological properties of mPFC glutamatergic and GABAergic neurons, regarding rest membrane potentials (B), action potential firing frequency (C), and halfwidth (D). (E) Typical example of a putative glutamatergic neuron from mPFC. Left, pyramidal shape of a mPFC glutamatergic neuron. Middle, multiple action potentials triggered by 1‐ms depolarizing current of 100 pA. Right, a typical single action potential from the neuron in left panel. (F) Typical example of a putative GABAergic neuron from mPFC. Left, oval shape of a mPFC GABAergic neuron. Middle, multiple action potentials triggered by 1 ms depolarizing current of 100 pA. Right, a single action potential from the neuron in left panel.

FIGURE 2

Distinct alterations in glutamatergic neuronal excitation between male and female rats. (A) Altered rest membrane potentials of mPFC glutamatergic neurons between male control and male MSEW group. (B) Altered threshold of a single action potential of mPFC glutamatergic neurons between male control and male MSEW group. (C) Increased amplitude of a single action potential of mPFC glutamatergic neurons in female MSEW group. (D) Multiple action potentials of 4 groups. Decreased number of APs between male groups. (E–H) Representative multiple action potentials of the 4 groups (*p < .05; **p < .01, MSEW group compared with control group. N = 10 cells for each group).

FIGURE 3

Distinct alterations in GABAergic neuronal excitation between male and female rats. (A) Altered rest membrane potentials of mPFC GABAergic neurons between female control and female MSEW group. (B) Altered threshold of a single action potential of mPFC GABAergic neurons between control and MSEW groups. (C) Increased amplitude of a single action potential of mPFC glutamatergic neurons in male MSEW group. (D) Multiple action potentials of 4 groups. Decreased number of APs in between male groups. (E–H) Representative multiple action potentials of the 4 groups (*p < .05; **p < .01; ****p < .0001, MSEW group compared with control group. N = 10 cells for each group).