Electrical properties of neocortical neurons in slices from children with intractable epilepsy

Abstract

1. The intrinsic electrical properties of human neocortical neurons were studied with current-clamp and single-electrode voltage-clamp techniques in slices obtained from children, aged 3 mo to 15 yr, undergoing surgical treatment of intractable epilepsy. Neocortical samples were classified as most or least abnormal based on clinical data. Recorded neurons were labeled with biocytin for correlation of electrical properties with morphological characteristics and laminar position. All recorded neurons were divided into three cell types--fast-spiking, low-threshold spiking (LTS) and non-LTS cells--on the basis of their electrical characteristics. 2. Fast-spiking cells generated brief, rapidly repolarizing action potentials. Most of these cells showed only weak spike-frequency adaptation. Fast-spiking cells labeled with biocytin were aspiny or sparsely spiny nonpyramidal neurons located in cortical layers 2-4. 3. LTS cells generated Ca(2+)-dependent low-threshold potentials and were the most numerous of the three cell types. Their Na(+)-dependent action potentials were broader than those of fast-spiking cells and showed marked spike-frequency adaptation. The size of low-threshold Ca2+ potentials and currents varied across cells, but they never supported more than two or, occasionally, three fast action potentials. LTS cells were pyramidal neurons located throughout cortical layers 2-6. Unlike the bursting neocortical cells described in lower mammals, LTS neurons in neocortex from children failed to generate bursts of inactivating Na+ action potentials. 4. Non-LTS cells also had relatively broad Na(+)-dependent action potentials and showed spike-frequency adaptation, but they did not generate detectable low-threshold potentials or currents. Non-LTS cells were also pyramidal neurons located throughout layers 2-6. 5. The electrical properties of cells from different age groups (< or = 1, 2-8, and 9-15 yr) and from most-abnormal and least-abnormal tissue samples were compared. A statistically significant trend toward a lower input resistance, a faster membrane time constant, and a decreased spike duration was observed with increasing age. There were no significant differences between the electrical properties of cells from the most-abnormal tissue and cells from the least-abnormal tissue. 6. These data indicate that the intrinsic electrical properties of neocortical neurons from children vary according to cell morphology and change with increasing age, as has been observed in rodent and feline neocortical neurons. No obvious evidence of epileptogenicity was detected in the intrinsic electrical properties of any of the neurons studied.

Cytomegalic Interneurons

“…Although the average frequencies reported here are not very high, we have to consider that firing rates were calculated at just above threshold and thus do not reflect the maximal frequency. At higher stimulation intensities some interneurons could reach frequencies greater than 100 Hz, consistent with human and animal studies (21,22). Some cytomegalic cells also showed decreased Na + spike inactivation.…”

“…Although these patterns can be very diverse (15), 3 general categories are accepted and include the fast-spiking, the low-threshold or burst spiking, and the regular-spiking interneurons. In a previous study using cortical slices from pediatric epilepsy patients, all interneurons were found to be fast-spiking (22). In our population, most normal-appearing and cytomegalic interneurons fired fast, repetitive action potentials with no or weak adaptation, either spontaneously or in response to depolarizing current injection and were considered fastspiking interneurons, which is consistent with their predominantly basket cell morphology.…”

Physiological properties of inhibitory interneurons in cat striate cortex

“…On the basis of previous in vitro studies (McCormick et al, 1985), we have focused our efforts on so called fast spiking (FS) cells that have at least three distinct intrinsic characteristics: very brief action potential duration, little or no spike frequency adaptation in response to Physiological Properties of Inhibitory Interneurons in Cat Striate Cortex intracellular depolarizing current injection, and a steep linear relationship between discharge frequency and amplitude of current injection. Cells having these properties have been shown to correlate well with the morphological characteristics of a subset of GABAergic interneurons, including basket cells and chandelier cells (McCormick et al, 1985;Naegele and Katz, 1990;Kawaguchi andKubota, 1993, 1997;Jones and Bühl 1993;Tasker et al, 1996). Here we determine the intrinsic membrane properties, responses to visual stimuli, receptive field properties, and selectivity for stimulus orientation and direction of fast spiking interneurons in the cat primary visual cortex.…”

“…Consequently the study of neocortical inhibitory interneurons has been largely restricted to the in vitro slice preparation. These studies have revealed the intrinsic electrophysiological properties of these neurons as well as their important role in the regulation of neuronal excitability (McCormick et al, 1985;Jones and Heinemann, 1988;Foehring et al, 1991;Llinàs et al, 1991;Jones and Bühl 1993;Kawaguchi, 1995;Chen et al, 1996a;Kawaguchi andKubota, 1996, 1997;Tasker et al, 1996;Thomson et al, 1996;Thomson and Deuchars, 1997). Although this technique has clear advantages for studying the cellular properties of interneurons, it has obvious limitations for investigating physiological function.…”

Subcircuit-specific neuromodulation in the prefrontal cortex

“…Recently, it has become evident that L5 PT and IT neurons within rodent PFC possess distinct intrinsic properties, local connectivity, and long-range inputs. Although most of these differences have been characterized in rodents, different categories of PFC pyramidal neurons are also present in humans and non-human primates (Foehring et al, 1991; Tasker et al, 1996; Chang and Luebke, 2007). PT and IT neuron categories can be further subdivided into groups based on gene expression, specific projection targets and laminar distribution.…”