Trends in Neurosciences
Interneuron Diversity seriesDiversity of inhibitory neurotransmission through GABAA receptors
Section snippets
Phasic (synaptic and ’perisynaptic’) inhibition
Synaptic GABAA receptors are anchored by specific proteins [9] of lesser renown than those found at synapses harboring glutamate receptors [10]. Nevertheless, just like glutamate receptors, the number of synaptic GABAA receptors is subject to large alterations during neuronal plasticity and development [11]. Synaptic GABAA receptors usually contain γ subunits, in particular γ2 [11], which is a key factor for benzodiazepine sensitivity [12]. Phasic (synaptic) GABA-mediated transmission 13, 14, 15
Tonic inhibition
Many cells display tonic currents activated by the near-micromolar GABA levels [21] always present in the extracellular space. The charge carried by the activation of tonically active GABAA receptors can be more than three times larger than that produced by phasic inhibition, even when the frequency of phasic events is large 22, 23, 24 (Figure 1). Experimental and theoretical studies indicate that a tonic GABA conductance produces a shunt that affects excitability and gain control [6]. Perhaps
Subunit composition of synaptic GABAA receptors
GABAA receptors are pentameric hetero-oligomers assembled from members of seven different subunit classes, some of which have multiple members: α(1–6), β(1–3), γ(1–3), δ, ε, θ and π [12]. In theory, a bewildering array of various combinations could assemble from these many subunits and their splice variants. However, GABAA receptor subunits do form preferred assemblies, with perhaps dozens of distinct subunit combinations actually present in the brain [12]. Studies in expression systems have
Concluding remarks
Many sources of physiological diversity have been discovered at GABA synapses (Figure 3), and it is likely that the list will grow. Will it be possible to identify the functional consequences of this diversity, and to what end will such information be useful? There is even more complexity because functional diversity per se can translate into higher-level network properties, when population variance as well as mean parameter values determine the behavior of interconnected neurons [68]. In fact,
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