Mechanisms of inhibition within the telencephalon: "where the wild things are"

Abstract

In this review, we first provide a historical perspective of inhibitory signaling from the discovery of inhibition through to our present understanding of the diversity and mechanisms by which GABAergic interneuron populations function in different parts of the telencephalon. This is followed by a summary of the mechanisms of inhibition in the CNS. With this as a starting point, we provide an overview describing the variations in the subtypes and origins of inhibitory interneurons within the pallial and subpallial divisions of the telencephalon, with a focus on the hippocampus, somatosensory, paleo/piriform cortex, striatum, and various amygdala nuclei. Strikingly, we observe that marked variations exist in the origin and numerical balance between GABAergic interneurons and the principal cell populations in distinct regions of the telencephalon. Finally we speculate regarding the attractiveness and challenges of establishing a unifying nomenclature to describe inhibitory neuron diversity throughout the telencephalon.

Figure 1

Key events in the discovery of inhibition.

Figure 2

(a) Immature neuron expressing the NKCC (sodium-potassium chloride cotransporter) transporter. NKCC uses the inward Na⁺ gradient maintained by the Na⁺ pump to transport Cl⁻ into the cell. This increases the intracellular Cl⁻ concentration, resulting in a chloride equilibrium potential (E_Cl) that is more positive than the membrane potential (V_m). GABA-mediated activation of GABA_A receptors at V_m produces Cl⁻ efflux, resulting in membrane depolarization. (b) Mature neuron coexpressing NKCC (sodium-potassium chloride) and KCC2 (sodium-potassium) cotransporters. KCC2 dominates over NKCC. KCC2 extrudes Cl⁻, lowering the intracellular Cl⁻ concentration, resulting in a chloride equilibrium potential (E_Cl) that is more negative than the membrane potential (V_m). GABA-mediated activation of GABA_A receptors at V_m produces Cl⁻ influx, resulting in membrane hyperpolarization.

Figure 3

Cross section of an adult brain: (left) the relative proportion of excitatory (green) or inhibitory (light red) principal projection neurons compared with the percentage of inhibitory interneurons in each of the illustrated structures; (right) the relative proportion of inhibitory interneurons within these same structures that are thought to be derived from the medial ganglionic eminence (MGE) (blue) or the caudal ganglionic eminence (CGE) (yellow). Abbreviations: CA1, CA1 region of the hippocampus; S1BF, primary somatosensory cortex/barrel field; PIR, piriform cortex; Str, striatum; BLA, basal-lateral amygdala; CEA, central amygdala nuclei; MEA, medial amygdala nuclei.