Short-term repeated corticosterone administration enhances glutamatergic but not GABAergic transmission in the rat motor cortex

Abstract

It has been demonstrated that stress impairs performance of skilled reaching and walking tasks in rats due to the action of glucocorticoids involved in the stress response. Skilled reaching and walking are controlled by the primary motor cortex (M1); however, it is not known whether stress-related impairments in skilled motor tasks are related to functional and/or structural alterations within the M1. We studied the effects of single and repeated injections of corticosterone (twice daily for 7 days) on spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) recorded from layer II/III pyramidal neurons in ex vivo slices of the M1, prepared 2 days after the last administration of the hormone. We also measured the density of dendritic spines on pyramidal cells and the protein levels of selected subunits of AMPA, NMDA, and GABAA receptors after repeated corticosterone administration. Repeatedly administered corticosterone induced an increase in the frequency but not in the amplitude of sEPSCs, while a single administration had no effect on the recorded excitatory currents. The frequency and amplitude of sIPSCs as well as the excitability of pyramidal cells were changed neither after single nor after repeated corticosterone administration. Treatment with corticosterone for 7 days did not modify the density of dendritic spines on pyramidal neurons. Corticosterone influenced neither the protein levels of GluA1, GluA2, GluN1, GluN2A, and GluN2B subunits of glutamate receptors nor those of α1, β2, and γ2 subunits of the GABAA receptor. The increase in sEPSCs frequency induced by repeated corticosterone administration faded out within 7 days. These data indicate that prolonged administration of exogenous corticosterone selectively and reversibly enhances glutamatergic, but not GABAergic transmission in the rat motor cortex. Our results suggest that corticosterone treatment results in an enhancement of spontaneous glutamate release from presynaptic terminals in the M1 and thereby uncovers a potential mechanism underlying stress-induced motor functions impairment.

Diverse action of repeated corticosterone treatment on synaptic transmission, neuronal plasticity, and morphology in superficial and deep layers of the rat motor cortex

“…Spines were counted on 76 segments of 14 layer II/III neurons of the corticosterone-treated group (total length of analyzed dendrites = 3079 μm) and on 76 segments of 16 layer II/III neurons of the control group (total length of analyzed dendrites = 3991.9 μm). Consistently with our previous report [ 23 ], the calculated average total dendritic spine density did not differ significantly between the corticosterone-treated and control group either in the apical (1.1 ± 0.1 vs. 1.0 ± 0.1 spines/μm, respectively, p = 0.38) or in the basal part of the dendritic tree (total: 1.0 ± 0.05 vs. 1.0 ± 0.1 spines/μm, respectively, p = 0.84). The density of each morphological spine type investigated (Fig.…”

“…Spontaneous EPSCs (sEPSCs) were recorded for 4 min from neurons which were voltage-clamped at −76 mV [ 23 ]. Then, the slices were superfused with ACSF containing 0.5 μM tetrodotoxin (TTX, Abcam).…”

“…We have recently demonstrated that repeated corticosterone administration for 7 days resulted in an increase in the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) recorded from layer II/III pyramidal neurons, which was not accompanied by changes in spontaneous inhibitory postsynaptic currents (sIPSCs) or the excitability of layer II/III pyramidal cells of rat M1 [ 23 ]. We also analyzed the density of dendritic spines on layer II/III pyramidal neurons but did not observe its change in corticosterone-treated animals [ 23 ].…”

“…We have recently demonstrated that repeated corticosterone administration for 7 days resulted in an increase in the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) recorded from layer II/III pyramidal neurons, which was not accompanied by changes in spontaneous inhibitory postsynaptic currents (sIPSCs) or the excitability of layer II/III pyramidal cells of rat M1 [ 23 ]. We also analyzed the density of dendritic spines on layer II/III pyramidal neurons but did not observe its change in corticosterone-treated animals [ 23 ]. Given that layers II/III and V pyramidal cells play different roles in receiving, integrating, and sending output from the M1, in the present study, we aimed to determine whether repeated corticosterone administration induces functional changes in M1 excitatory synaptic transmission in layer V pyramidal neurons, similar to those observed in layer II/III pyramidal cells [ 4 , 23 ].…”

“…We also analyzed the density of dendritic spines on layer II/III pyramidal neurons but did not observe its change in corticosterone-treated animals [ 23 ]. Given that layers II/III and V pyramidal cells play different roles in receiving, integrating, and sending output from the M1, in the present study, we aimed to determine whether repeated corticosterone administration induces functional changes in M1 excitatory synaptic transmission in layer V pyramidal neurons, similar to those observed in layer II/III pyramidal cells [ 4 , 23 ]. Moreover, we compared the amplitudes of field potentials evoked in intralaminar connections within layers II/III and V. We also assessed the potential of these connections to undergo synaptic plasticity using chemically induced long-term potentiation (chemLTP) by tetraethylammonium (TEA), which is a reliable model of VDCC-dependent synaptic plasticity induction within M1 acting through protein kinase A (PKA) and the extracellular signal-regulated kinase 1/2 (ERK1/2) cascade [ 14 , 19 ].…”