15 research outputs found

    Interaction of HIV-1 aspartic protease with its inhibitor, by molecular dynamics and ab initio

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    The role of GABAergic inputs for coincidence detection in the neurones of nucleus laminaris of the chick

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    Synaptic inputs to nucleus laminaris (NL) neurones were studied in a brainstem slice preparation of chick embryos (E15–20) using the whole-cell patch clamp technique. NL neurones are third order auditory neurones and are proposed to behave as coincidence detectors concerned with interaural timing discrimination.Under voltage clamp conditions, electrical stimuli applied to either ventral or dorsal dendritic layers evoked EPSCs. These fast currents decayed with a time constant of 1.1 ms near the resting potential, reversed close to 0 mV, and were blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 20 μM) or 6,7-dinitro-quinoxaline-2,3-dione (DNQX, 20 μM). Coincident or near coincident stimulation of the ventral and the dorsal dendritic layers increased the probability of action potential generation (response probability).In the presence of CNQX (40 μM) other postsynaptic currents (PSCs) were observed, which reversed close to the equilibrium potential for chloride (ECl), and were reversibly blocked by bicuculline (20 μM) and, therefore, were mediated by GABAA receptors. Spontaneous GABAergic PSCs were inward going near the resting membrane potential immediately after starting whole-cell recording with a low Cl− (5 mM, ECl = −90 mV) pipette medium, but became outward-going with time. This indicates that GABAergic inputs may generate depolarizing potentials in intact NL neurones.Local GABA (10 μM) application reduced both the EPSP and EPSC amplitude and shortened the EPSP decay time constant (from 5.3 to 2.1 ms), while the EPSC decay time constant was not affected (from 1.3 to 1.2 ms). These GABA effects were mostly due to the shunting conductance of the postsynaptic GABAA receptors.Depolarizing current injections combined with electrical stimuli to a unilateral axon bundle simulated bilateral synaptic inputs. Response probability increased with decreased interstimulus intervals, while local GABA (10 μM) application to the soma narrowed the time dependence of the response probability.These results suggest that GABAergic inputs to NL neurones may serve to improve coincidence detection of the bilateral excitatory inputs through an increase in membrane conductance
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