GABAergic inhibition in the neostriatum
Section snippets
Most striatal neurons are GABAergic, but most striatal synapses are not
The striatum apparently possesses no native species of excitatory neuron. With the exception of the cholinergic interneuron, all the cell types so far identified in the striatum are GABAergic, and presumably inhibitory in function. This includes both interneurons and the principal cells. The abundant principal neurons of the striatum, the spiny (Sp) cells, which constitute the vast majority of the neurons, are of two types. The two subclasses are present in approximately equal proportions and
Spatial distribution of GABAergic synapses on spiny cells
It would be useful to know how many GABAergic synapses there are on each Sp projection neuron, and what proportion of these originates from interneurons and what from other projection cells. GABAergic axons arising from the Sp cells and interneurons form symmetrical synapses. Symmetrical contacts account for about 20% of all synapses in the striatum (Ingham et al., 1998). Assuming that most of these are on Sp cells, it would suggest that there are about 2500 symmetrical synapses per Sp cell.
How can inhibition be effective when so outnumbered?
If inhibition is to be effective in controlling the effects of the massive excitatory innervation of the Sp cell, it must be either because few excitatory inputs are active at any one time, or because inhibitory synapses are given some advantage over excitation, for example a larger or more long-lived conductance change, a higher probability of transmitter release, or a more advantageous location on the neuron. The effectiveness of synapses formed by GABAergic interneurons may rely in part on
Feedforward and feedback inhibition
Feedback and feedforward inhibition are separated in the striatum by the inhibitory nature of the Sp cell. Although collaterals of the Sp cells may make synaptic contacts with FS and SOM interneurons and so may influence the feedforward pathways, they do not excite those cells and so cannot evoke lateral inhibition through that pathway. The Sp cells, via their connections among each other, exclusively control feedback inhibition. To be faithful to the original meaning of these words,
Winner-take-all inhibition in the striatum?
Feedback inhibition has often been proposed to play an important functional role in the striatum (e.g., Wickens, 1993; Rolls and Treves, 1998; Plenz and Kitai, 2000; Bar-Gad and Bergman, 2001). Feedback inhibition can offer a powerful computational advantage in a network of neurons receiving a common set of afferents, and having a mechanism of use-dependent synaptic plasticity in the input pathway. If the inhibition is strong enough to limit the number of neurons that can respond to any one
Could groups of spiny cells compete with each other?
Starting with the Tunstall et al. (2002) paper, an effort was made to measure the connectivity among Sp cells. The results consistently showed a connectivity of about 0.16, that is, any particular Sp neuron is found to make synapses with about 1/6 of its nearby neighbours. This high connectivity indicates that every Sp neuron receives many synapses from other Sp neurons. Assuming an axonal field of about 400 μm diameter, and a connectivity of 1/6, each Sp neuron would receive synapses from about
Inhibition and the mechanism of up and down states in vivo
In vivo, the membrane potentials of Sp neurons transition between the Up and Down states under the influence of synaptic inputs. In unanesthetized animals, the transitions are irregular, and cells can spend minutes in the Down state (Wilson and Groves, 1981). In animals anesthetized with urethane, or with ketamine, highly organized slow rhythmic changes in cortical activity imposes similar slow changes in Sp neurons, making it relatively easy to study these transitions (Wilson and Kawaguchi,
Why is Sp→Sp inhibition so weak?
Although the functional implications of fast, powerful and non-convergent feedforward inhibition and weak convergent feedback are not known, we do know the cellular reasons why the strengths of FS→Sp and Sp→Sp synapses are so different. Kóos et al. (2004) studied the reasons for the strength of FS→Sp cell synapses, using quantal analysis to compare the synapses on Sp cells derived from FS cells to the weaker synapses formed by Sp cells. These experiments showed that the conductance change
The reversal potential of GABAA
The reversal potential of GABAA inhibition in Sp cells has repeatedly been shown to be positive to the resting potential, and negative to the action potential threshold, resulting in depolarizing IPSPs when measured in slices at the resting potential (Misgeld et al., 1982; Plenz, 2003; Bracci and Panzeri, 2006). Measurements of the reversal potential of GABAA IPSCs in gramicidin perforated patch recordings in slices have confirmed that the chloride equilibrium potential in Sp neurons lies
Dendritic inhibition probably acts in the dendrites
Although the inhibition exerted by Sp cell synapses is small when viewed from the Sp cell soma, it is very large at locations in the dendrite near the synapse. Possibly, the large local IPSPs generated by these synapses may exert a function not fully appreciated from the soma, or from the site of action potential generation. One possible dendritic effect of inhibition is suggested by the nonlinear membrane characteristics of the cell in the subthreshold range. As described above, the membrane
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