Trends in Neurosciences
Volume 27, Issue 11, November 2004, Pages 662-669
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GABAergic microcircuits in the neostriatum

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The vast majority of neostriatal neurons and intrinsic intrastriatal synapses are GABAergic, the latter arising from axon collaterals of spiny projection neurons and from GABAergic interneurons. An important feature of the functional organization of the neostriatum has long been assumed to be the existence of a widespread lateral inhibitory network mediated by the axon collaterals of spiny projection neurons. However, these collateral connections have recently been demonstrated electrophysiologically to be relatively weak – in contrast to feedforward interneuronal inhibition, which exerts strong effects on spike timing in spiny neurons. These new data are incompatible with current ‘winner-take-all’ models of lateral inhibitory function in the neostriatum, and they force a modification of established concepts of the functional roles of feedback inhibition in this nucleus.

Section snippets

GABA-mediated inhibition in neostriatum

Neostriatal spiny neurons are characterized by a dense and extensive local axon collateral field that usually extends over a volume similar to or slightly larger than the dendritic arborization of the parent neuron [10] (Figure 1a). Early intracellular labeling studies revealed that the principal targets of these axon collaterals were other spiny neurons 11, 12 (Figure 1b). It was logical to assume that this local axon collateral plexus was the substrate for a powerful lateral inhibitory

Feedforward inhibition through GABAergic interneurons

The best-characterized striatal GABAergic interneuron is the parvalbumin-containing interneuron. It belongs to a class of cells that exist in the neocortex, hippocampus and elsewhere that are classified as fast-spiking (FS) interneurons 24, 25, 26. These neurons exhibit brief action potentials, large and rapidly peaking spike afterhyperpolarizations, and relatively linear current–voltage curves. Although capable of sustained activity at >200 Hz with little or no spike-frequency adaptation, more

Feedback inhibition through spiny neuron axon collaterals

Tunstall et al. [34] were the first to demonstrate inhibitory interactions between spiny neurons with intracellular current-clamp recordings from pairs of spiny neurons in slices taken from mature rats. The collateral IPSPs were small (mean 277±46 μV, excluding failures) and only reliably detected by averaging hundreds of sweeps. They exhibited a variable but fairly high failure rate (38±14%). The fact that the synaptic interactions among spiny neurons are so weak and prone to failure explains

What accounts for the differences in synaptic strength between feedforward and feedback inhibition?

When measured in identical preparations under the same recording conditions, the spiny neuron collateral IPSC is only between one-quarter and one-sixth the amplitude of the interneuron–spiny neuron IPSC measured at the soma 29, 37 (Figure 4). Although it is more difficult to compare the relative amplitudes of the two IPSPs or IPSCs quantitatively, estimates based on other reports consistently indicate that the amplitude of the collateral synaptic response is smaller than that of the

Functional roles of interneuronal and axon collateral inhibition in neostriatum

In contrast to original expectations based on anatomical observations [11], but consistent with subsequent predictions from electrophysiological studies 20, 23, most GABA-mediated control of spiking in spiny neurons appears to involve striatal interneurons (even though there are many times more spiny neuron collateral synapses than interneuron–spiny cell synapses). The interneurons exert powerful inhibition; even a single spike in one interneuron can delay or prevent spiking in a spiny neuron.

Concluding remarks

The original concept of the neostriatum as a large ‘winner-takes-all’ lateral inhibitory network is no longer viable because of the weakness of individual collateral synapses and the lack of reciprocal connectivity. Interneuronal inhibition, however, is strong and likely to play a major role in regulating spike timing. Both concepts need to be incorporated into the next generation of computational models of neostriatal function. The operational characteristics of the neostriatal axon collateral

Acknowledgements

Our research was supported by NS34865 and a Busch Biomedical Research Support Grant (to J.M.T.) and NS20743 (to C.J.W.).

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