Trends in Neurosciences
Volume 26, Issue 8, August 2003, Pages 436-443
Journal home page for Trends in Neurosciences

When inhibition goes incognito: feedback interaction between spiny projection neurons in striatal function

https://doi.org/10.1016/S0166-2236(03)00196-6Get rights and content

Abstract

Theories about basal ganglia function have always been driven by our knowledge about the spiny projection neurons of the striatum. At the core of these theories lies the question of how, precisely, spiny projection neurons process cortical inputs. Most recently, studies demonstrating the role of spiny projection neurons in local synaptic GABA transmission have provided several new avenues for exploring striatal dynamics. They have also suggested new experimental directives for examining the specific ways in which spiny projection neurons both compete and cooperate through their local axon collaterals during cortical input processing.

Section snippets

Lateral inhibition in striatal theory and function

This more recent idea of intrastriatal GABA transmission being dominated by striatal interneurons stands in stark contrast to most previously existing models of corticostriatal processing. The striatum, despite its actual three-dimensionality, has mostly been understood to function somewhat like a two-dimensional neuronal sheet. Spiny projection neurons receive most of their excitatory inputs from cortex and then directly project out of the nucleus (reviewed in Refs 23, 24), the shortest

GABA-mediated synaptic transmission between spiny projection neurons

In an attempt to account more fully for this complexity, two recent studies have examined monosynaptic transmission between spiny projection neurons using different techniques. Using sharp intracellular electrodes, Tunstall et al. [43] found a fast monosynaptic connection between spiny projection neurons in mature striatal slices in seven out of 90 spiny-projection-neuron pairs. This synaptic connection was depolarizing at rest, with a peak amplitude of ∼0.1 mV at an average input resistance of

A role for cooperative interaction between spiny projection neurons

Mature spiny projection neurons possess a highly polarized resting membrane potential at ∼−80 to −90 mV [45]. Thus, it was not particularly surprising when early testing for the action of GABAA-receptor activation found GABA responses to be depolarizing at rest and usually reversed between −60 and −50 mV (the equilibrium potential of Cl, ECl), whether measured in the acute slice 43, 46 or in vivo with extracellularly applied GABA [47]. The relatively depolarized ECl introduces a membrane

From ‘winner-take-all’ to precise time delays in postsynaptic neurons

A ‘winner-take-all’ dynamic has typically been applied to striatal neural network models to explain the unique selection of an action among multiple alternatives in spiny-projection-neuron interactions [53]. In its simplest form (i.e. for a network with mutual inhibitory connections), the neuron that fires most strongly will inhibit all other postsynaptic neurons. Such a dynamic can be observed in mutually coupled spiny projection neurons (Fig. 4), suggesting that it can explain selection among

Short-term plasticity in striatal GABA transmission and function

The high failure rate in synaptic transmission between spiny projection neurons seems to suggest that relatively weak lateral interaction takes place between these neurons. However, it has been shown that synaptic transmission drastically changes in response to repetitive activation [41]. Indeed, postsynaptic depolarization in spiny projection neurons displays striking short-term plasticity in response to presynaptic action potential bursts at different frequencies (Fig. 6a). Using

Sparse connectivity between striatal spiny projection neurons

Models of lateral inhibition commonly assume a symmetrical lateral connectivity among neurons, in which each neuron is connected to most (if not all) of its neighbors [26]. The experimental findings, however, suggest a connectivity among spiny projection neurons that is instead sparse and highly asymmetrical. Because the local axonal field of any given spiny projection neuron overlaps with its parental dendritic tree, the probability P of finding a synaptic connection declines with the distance

The striatum as a resistor network coupled through gap junctions

Dye-coupling experiments have suggested that spiny projection neurons might communicate further through gap junctions regulated by dopamine and nitric oxide 74, 75, 76, 77. Such coupling can be seen in young striatal slices but is absent in mature striatal cultures [44]. It is possible that gap junctions might be revealed only under conditions of high-input activity [77]. Under conditions of strong electronic coupling, the striatum could function as a resistive grid that readily computes state

Concluding remarks and future directions

The discovery that functional synaptic transmission takes place between spiny projection neurons introduces feedback interaction into striatal dynamics as a fundamental mechanism in the processing of cortical inputs. It thus re-establishes a key element of earlier models that viewed the striatum as a lateral inhibitory network. However, the complexity of the dynamics of synaptic transmission suggests additional dimensions for this feedback circuitry that have yet to be explored fully. Its role

Acknowledgements

I thank Kim Blackwell, Uwe Czubayko, Chip Gerfen, Jason Kerr and Steve Wise for their helpful comments during writing of this article. This work is supported by DIRP.

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