Neuronal excitability and spontaneous synaptic transmission in the entorhinal cortex of BDNF heterozygous mice

Abstract

Brain Derived Neurotropic Factor (BDNF) is a neutrophic factor that is required for the normal neuronal development and function. BDNF is involved in regulation of synapses as well as neuronal excitability. Entorhinal Cortex (EC) is a key brain area involved in many physiological and pathological processes. In this study we investigated the effects of chronically reduced BDNF levels on layer 3 pyramidal neurons of EC. We aimed to assess the effects of reduced levels of BDNF on firing properties, spontaneous synaptic currents and excitation/inhibition balance from acute brain slices. Patch clamp recordings were obtained from pyramidal neurons of Entorhinal Cortex Layer 3. Findings of BDNF heterozygous (BDNF (+/-)) mice compared to their wild-type littermates at the age of 23-28 days. Action potential threshold was shifted (p = 0,002) to depolarized potentials and spike frequency was smaller in response to somatic current injection steps in BDNF (+/-) mice. Spontaneous synaptic currents were also affected. sEPSC amplitude (p = 0,009), sIPSC frequency (p = 0,001) and sIPSC amplitudes (p = 0,023) were reduced in BDNF (+/-). Decay times of sIPSCs were longer in BDNF (+/-) (p = 0,014). Calculated balance of excitatory/inhibitory balance was shifted in the favor of excitation in BDNF (+/-) mice (p = 0,01). These findings suggest that reductions in concentrations of BDNF results in altered status of excitability and excitation/inhibition imbalance. However, these differences observed in BDNF (+/-) seem to have opposing effects on neuronal activity.

Keywords: BDNF; BDNF heterozygous mice; Entorhinal Cortex; Firing properties; Synaptic transmission.