Modulation of allopregnanolone on excitatory transmitters release from single glutamatergic terminal

作者：Iwata Satomi; Wakita Masahito; Shin Min Chul^*; Fukuda Atsuo; Akaike Norio

来源：Brain Research Bulletin, 2013, 93: 39-46.

DOI：10.1016/j.brainresbull.2012.11.002

• Rat CA3 neuron
• Glutamatergic terminal
• GABA(A) receptor
• Allopregnanolone
• Synaptic bouton preparation

Neurosteroids such as allopregnanolone (Allo) are widely distributed in the brain and may modulate neuronal excitability under physiological or pathological states. Allo modulates GABA(A) receptor responses, and in this study we investigated the functional effects of Allo on presynaptic GABA(A) receptors on single glutamatergic nerve terminal projecting on CA3 neurons. In the present study, we measured spontaneous and evoked excitatory postsynaptic currents (sEPSCs and eEPSCs), the latter was elicited with single or paired-pulse focal electrical stimulation, using mechanically isolated %26apos;synaptic bouton%26apos; preparation. Allo (10 nM) increased significantly eEPSC amplitude while decreasing the failure rate (R-f) and the paired-pulse response ratio (PPR). Conversely high concentration (100 nM) of Allo decreased eEPSC amplitude and increased R-f and PPR. Allo also increased significantly the frequency and amplitude of sEPSCs at low concentrations (10-30 nM) but at high concentration (100 nM) it had no effect on current amplitude but modestly decreased sEPSC frequency. Application of Allo at nanomolar concentrations facilitated exogenous muscimol-induced outward postsynaptic currents but had no effect on glutamate-induced inward postsynaptic currents. Our results demonstrate that Allo modulates glutamate release via presynaptic GABA(A) receptors, in addition to its better characterized effects to modulate postsynaptic GABA(A) responses. Both pre- and postsynaptic GABA(A) receptor modulation is likely to contribute to the physiological actions of neurosteroids.

• 出版日期2013-4