Journal of neurophysiology
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Although 3alpha-substituted metabolites of progesterone are well established to interact with GABA(A) receptor/Cl(-) channels, the nature of the interaction(s) remains uncertain. We used patch-clamp recording to study the interaction with GABA(A) receptor/Cl(-) channels expressed by embryonic hippocampal neurons differentiating in culture and nonneuronal cells transfected with GABA(A) receptor subunits. Allopregnanolone primarily induced multiphasic current responses in neurons, which were eliminated by bicuculline, an antagonist of GABA at GABA(A) receptor/Cl(-) channels. ⋯ Pertussis toxin treatment eliminated the low-amplitude current and attenuated the high-amplitude current induced by allopregnanolone in a reversible manner. Mastoparan, which activates G proteins directly, triggered a high-amplitude current after a delay, which was blocked by bicuculline. The results indicate that allopregnanolone interacts with GABA(A) receptor/Cl(-) channels expressed by embryonic hippocampal neurons in multiple ways, some of which are mediated by G proteins.
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During early neuronal development, GABA functions as an excitatory neurotransmitter, triggering membrane depolarization, action potentials, and the opening of plasma membrane Ca(2+) channels. These excitatory actions of GABA lead to a number of changes in neuronal structure and function. Although the effects of GABA on membrane biophysics during early development have been well documented, little work has been done to examine the possible mechanisms underlying GABA-regulated plastic changes in the developing brain. ⋯ BDNF (100 ng/ml) dramatically increased the frequency of excitatory GABAergic spontaneous postsynaptic currents. Together, these data suggest a positive excitatory feedback loop between GABA and BDNF expression during early development, where GABA facilitates BDNF expression, and BDNF facilitates the synaptic release of GABA. Signaling via the MAPK cascade and the transcription factor CREB appear to play a substantial role in this process.
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Uninjured C-type rat dorsal root ganglion (DRG) neurons predominantly express slowly inactivating TTX-resistant (TTX-R) and slowly repriming TTX-sensitive (TTX-S) Na(+) currents. After peripheral axotomy, TTX-R current density is reduced and rapidly repriming TTX-S currents emerge and predominate. The change in TTX-S repriming kinetics is paralleled by an increase in the level of transcripts and protein for the Na(v)1.3 sodium channel alpha-subunit, which is known to exhibit rapid repriming. ⋯ We observed parallel effects of GDNF and NGF on the Na(v)1.3 sodium channel transcript levels in axotomized DRG. Both GDNF and NGF were able to partially reverse the axotomy-induced increase in Na(v)1.3 mRNA, with GDNF plus NGF producing the largest effect. Our data indicate that both GDNF and NGF can partially reverse an important effect of axotomy on the electrogenic properties of sensory neurons and that their effect is additive.
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This research was guided by the working hypothesis that the aging auditory system progressively loses its ability to process rapid acoustic transients efficiently, and in elderly listeners, this results in difficulties in speech perception. Neural correlates of age-related deficits in temporal processing were investigated by recording from inferior colliculus (IC) neurons from young adult and old CBA mice. Single-unit responses were recorded to sinusoidally amplitude-modulated (SAM) noise carriers, presented at 65-80 dB SPL, having modulation frequencies (MFs) that ranged from 10 to 800 Hz. ⋯ The magnitude of the differences between the young adult and the old spike median responses was greatest at low MFs and then declined as MF increased. Finally, the young adult distribution of rBMFs extends to higher MFs than the old, with 36.0% of units having rBMFs >100 Hz as compared with only 12.5% of the old unit sample. We postulate that this age-related difference in rate coding of SAM noise carriers is consistent with a loss, or imbalance, of excitatory and inhibitory neural mechanisms known to shape encoding of envelope periodicities in the IC.
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Properties of GABA(A) receptor-mediated unitary inhibitory postsynaptic currents (uIPSCs) in pyramidal (P) cells, evoked by fast spiking (FS) and low-threshold spike (LTS) subtypes of interneurons in layer V of rat visual cortex slices were examined using dual whole cell recordings. uIPSCs evoked by FS cells were larger and faster rising than those evoked by LTS cells, consistent with the known primary projections of FS and LTS cell axons to perisomatic and distal dendritic areas of layer V pyramidal cells, respectively, and the resulting electrotonic attenuation for LTS-P synaptic events. Unexpectedly, the decay time constants for LTS-P and FS-P uIPSCs were not significantly different. Modeling results were consistent with differences in the underlying GABA(A) receptor-mediated conductance at LTS-P and FS-P synapses. ⋯ Short, 20-Hz trains of action potentials in presynaptic interneurons evoked trains of uIPSCs with exponentially decreasing amplitudes at both FS-P and LTS-P synapses. FS-P uIPSC amplitudes declined more slowly than those of LTS-P uIPSCs. Thus FS and LTS cells, with their differences in firing properties, synaptic connectivity with layer V P cells, and short-term synaptic dynamics, might play distinct roles in regulating the input-output relationship of the P cells.