The efficient propagation of action potentials along nervous fibers is necessary for animals to interact with the environment with timeliness and precision. Myelination of axons is an essential step to ensure fast action potential propagation by saltatory conduction, a process that requires highly concentrated voltage-gated sodium channels at the nodes of Ranvier. Recent studies suggest that the clustering of sodium channels can influence axonal impulse conduction in both myelinated and unmyelinated fibers, which could have major implications in disease, particularly demyelinating pathology. This comprehensive review summarizes the mechanisms governing the clustering of sodium channels at the peripheral and central nervous system nodes and the specific roles of their clustering in influencing action potential conduction. We further highlight the classical biophysical parameters implicated in conduction timing, followed by a detailed discussion on how sodium channel clustering along unmyelinated axons can impact axonal impulse conduction in both physiological and pathological contexts.

In the CA3 region of the hippocampus, pyramidal cells excite other pyramidal cells and interneurons. The axons of CA3 pyramidal cells spread throughout most of the region to form an associative network. These connections were first drawn by Cajal and Lorente de No. Their physiological properties were explored to understand epileptiform discharges generated in the region. Synapses between pairs of pyramidal cells involve one or few release sites and are weaker than connections made by mossy fibres on CA3 pyramidal cells. Synapses with interneurons are rather effective, as needed to control unchecked excitation. We examine contributions of recurrent synapses to epileptiform synchrony, to the genesis of sharp waves in the CA3 region and to population oscillations at theta and gamma frequencies. Recurrent connections in CA3, as other associative cortices, have a lower connectivity spread over a larger area than in primary sensory cortices. This sparse, but wide-ranging connectivity serves the functions of an associative network, including acquisition of neuronal representations as activity in groups of CA3 cells and completion involving the recall from partial cues of these ensemble firing patterns.

Neurotransmitters affect the membrane potential (V_m) of target cells by modulating the activity of receptor-linked ion channels. The direction and amplitude of the resulting transmembrane current depend on the resting level ofV_mand the gradient across the membrane of permeant ion species.V_m, in addition, governs the activation state of voltage-gated channels. Knowledge of the exact level ofV_mis therefore crucial to evaluate the nature of the neurotransmitter effect. However, the traditional methods to measureV_m, with microelectrodes or the whole-cell current-clamp technique, have the drawback that the recording pipette is in contact with the cytoplasm, and dialysis with the pipette solution alters the ionic composition of the interior of the cell. Here we describe a novel technique to determine theV_mof an intact cell from the reversal potential of K⁺currents through a cell-attached patch. Applying the method to interneurons in hippocampal brain slices yielded more negative values forV_mthan subsequent whole-cell current-clamp measurements from the same cell, presumably reflecting the development of a Donnan potential between cytoplasm and pipette solution in the whole-cell mode. Cell-attachedV_mmeasurements were used to study GABAergic actions in intact CA1 interneurons. In 1- to 3-week-old rats, bath-applied GABA inhibited these cells by stabilizingV_mat a level depending on contributions from both GABA_Aand GABA_Bcomponents. In contrast, in 1- to 4-d-old animals, only GABA_Areceptors were activated resulting in a depolarizing GABA response.