Trends in Neurosciences
When inhibition goes incognito: feedback interaction between spiny projection neurons in striatal function
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.
References (80)
- et al.
Immunocytochemical studies of GABAergic neurons in rat basal ganglia and their relationships to other neuronal systems
Neurosci. Lett.
(1984) Neuronal mechanism underlying dystonia induced by bicuculline injection into the putamen of the cat
Brain Res.
(1995)Local stimulation induced GABAergic response in rat striatal slice preparations: intracellular recordings on QX-314 injected neurons
Brain Res.
(1985)Striatal interneurons: chemical, physiological and morphological characterization
Trends Neurosci.
(1995)A theory of the functional organization of the neostriatum and the neostriatal control of voluntary movement
Brain Res.
(1983)- et al.
Analysis of striatal dynamics: the existence of two modes of behaviour
J. Theor. Biol.
(1993) - et al.
Stepping out of the box: information processing in the neural networks of the basal ganglia
Curr. Opin. Neurobiol.
(2001) Facilitation, augmentation and potentiation at central synapses
Trends Neurosci.
(2000)Molecular frequency filters at central synapses
Prog. Neurobiol.
(2000)Glutamatergic and GABAergic postsynaptic responses of striatal spiny neurons to intrastriatal and cortical stimulation recorded in slice preparations
Neuroscience
(1996)