ABSTRACT
The linear-nonlinear cascade model (LN model) has proven very useful in representing a neural system's encoding properties, but has proven less successful in reproducing the firing patterns of individual neurons whose behavior is strongly dependent on prior firing history. While the cell's behavior can still usefully be considered as feature detection acting on a fluctuating input, some of the coding capacity of the cell is taken up by the increased firing rate due to a constant "driving" direct current (DC) stimulus. Furthermore, both the DC input and the post-spike refractory period generate regular firing, reducing the spike-timing entropy available for encoding time-varying fluctuations. In this paper, we address these issues, focusing on the example of motoneurons in which an afterhyperpolarization (AHP) current plays a dominant role regularizing firing behavior. We explore the accuracy and generalizability of several alternative models for single neurons under changes in DC and variance of the stimulus input. We use a motoneuron simulation to compare coding models in neurons with and without the AHP current. Finally, we quantify the tradeoff between instantaneously encoding information about fluctuations and about the DC.
Subject(s)
Action Potentials/physiology , Models, Neurological , Neurons/physiology , Animals , Biophysics , Female , In Vitro Techniques , Male , Nonlinear Dynamics , Patch-Clamp Techniques , Rats , Rats, Sprague-DawleyABSTRACT
BACKGROUND AND PURPOSE: Tobacco and alcohol are often co-abused producing interactive effects in the brain. Although nicotine enhances memory while ethanol impairs it, variable cognitive changes have been reported from concomitant use. This study was designed to determine how nicotine and alcohol interact at synaptic sites to modulate neuronal processes. EXPERIMENTAL APPROACH: Acute effects of nicotine, ethanol, and both drugs on synaptic excitatory glutamatergic and inhibitory GABAergic transmission were measured using whole-cell recording in hippocampal CA1 pyramidal neurons from brain slices of mice on control or nicotine-containing diets. KEY RESULTS: Acute nicotine (50 nM) enhanced both GABAergic and glutamatergic synaptic transmission; potentiated GABA(A) receptor currents via activation of α7* and α4ß2* nAChRs, and increased N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor currents through α7* receptors. While ethanol (80 mM) also increased GABA(A) currents, it inhibited NMDA currents. Although ethanol had no effect on AMPA currents, it blocked nicotine-induced increases in NMDA and AMPA currents. Following chronic nicotine treatment, acute nicotine or ethanol did not affect NMDA currents, while the effects of GABAergic responses were not altered. CONCLUSIONS AND IMPLICATIONS: Acute ethanol ingestion selectively attenuated nicotine enhancement of excitatory glutamatergic NMDA and AMPA receptor function, suggesting an overall reduction in excitatory output from the hippocampus. It also indicated that ethanol could decrease the beneficial effects of nicotine on memory performance. In addition, chronic nicotine treatment produced tolerance to the effects of nicotine and cross-tolerance to the effects of ethanol on glutamatergic activity, leading to a potential increase in the use of these drugs.
Subject(s)
CA1 Region, Hippocampal/drug effects , Central Nervous System Depressants/pharmacology , Ethanol/pharmacology , Nicotine/pharmacology , Nicotinic Agonists/pharmacology , Pyramidal Cells/drug effects , Receptors, GABA-A/metabolism , Receptors, Glutamate/metabolism , Animals , CA1 Region, Hippocampal/metabolism , Central Nervous System Depressants/administration & dosage , Central Nervous System Depressants/metabolism , Ethanol/administration & dosage , Ethanol/metabolism , Excitatory Postsynaptic Potentials/drug effects , In Vitro Techniques , Inhibitory Postsynaptic Potentials/drug effects , Male , Mice , Mice, Inbred C57BL , Nicotine/administration & dosage , Nicotine/metabolism , Nicotinic Agonists/administration & dosage , Nicotinic Agonists/metabolism , Patch-Clamp Techniques , Receptors, AMPA/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Synaptic Transmission/drug effects , Time FactorsABSTRACT
Voltage-dependent persistent inward currents (PICs) make an important contribution to the input-output properties of alpha motoneurons. PICs are thought to be mediated by membrane channels located primarily on the dendrites as evidenced by prolonged tail currents following the termination of a voltage step and by a clockwise hysteresis in the whole cell inward currents recorded in response to depolarizing then repolarizing voltage ramp commands. We report here, however, that voltage-clamp currents with these same features can be generated in isolated somatic membrane patches from rat hypoglossal motoneurons. Long-lasting (200-800 ms) tail currents after 1-s voltage-clamp pulses were observed in nucleated patches from 16 of 23 cells. Further, these somatic PICs display "facilitation" in response to conditioning depolarization as previously observed in whole cell recordings from intact neurons. Pharmacological tests suggest that the PICs were primarily mediated by Cav1 channels. Our results show that many of the features of persistent calcium currents recorded from intact motoneurons do not necessarily reflect a remote dendritic origin but can also be ascribed to the intrinsic properties of their Cav1 channels.
