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Reconstructing the three-dimensional GABAergic microcircuit of the striatum.

Humphries MD, Wood R, Gurney K - PLoS Comput. Biol. (2010)

Bottom Line: From these, we found the probabilities of intersection between the neurites of two neurons given their inter-somatic distance, and used these to construct three-dimensional striatal networks.We show that both properties influence striatal dynamics: the most potent inhibition of a MSN arises from a region of striatum at the edge of its dendritic field; and the combination of local gap junction and distal synaptic networks between FSIs sets a robust input-output regime for the MSN population.Our models thus intimately link striatal micro-anatomy to its dynamics, providing a biologically grounded platform for further study.

View Article: PubMed Central - PubMed

Affiliation: Adaptive Behaviour Research Group, Department of Psychology, University of Sheffield, Sheffield, United Kingdom. m.d.humphries@shef.ac.uk

ABSTRACT
A system's wiring constrains its dynamics, yet modelling of neural structures often overlooks the specific networks formed by their neurons. We developed an approach for constructing anatomically realistic networks and reconstructed the GABAergic microcircuit formed by the medium spiny neurons (MSNs) and fast-spiking interneurons (FSIs) of the adult rat striatum. We grew dendrite and axon models for these neurons and extracted probabilities for the presence of these neurites as a function of distance from the soma. From these, we found the probabilities of intersection between the neurites of two neurons given their inter-somatic distance, and used these to construct three-dimensional striatal networks. The MSN dendrite models predicted that half of all dendritic spines are within 100µm of the soma. The constructed networks predict distributions of gap junctions between FSI dendrites, synaptic contacts between MSNs, and synaptic inputs from FSIs to MSNs that are consistent with current estimates. The models predict that to achieve this, FSIs should be at most 1% of the striatal population. They also show that the striatum is sparsely connected: FSI-MSN and MSN-MSN contacts respectively form 7% and 1.7% of all possible connections. The models predict two striking network properties: the dominant GABAergic input to a MSN arises from neurons with somas at the edge of its dendritic field; and FSIs are inter-connected on two different spatial scales: locally by gap junctions and distally by synapses. We show that both properties influence striatal dynamics: the most potent inhibition of a MSN arises from a region of striatum at the edge of its dendritic field; and the combination of local gap junction and distal synaptic networks between FSIs sets a robust input-output regime for the MSN population. Our models thus intimately link striatal micro-anatomy to its dynamics, providing a biologically grounded platform for further study.

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The striatal GABAergic microcircuit studied in this paper.Primary input to the striatum comes from glutamatergic (GLU: ) fibres originating in the neocortex, thalamus, hippocampal formation and amygdala, and dopaminergic (DA: ▪) fibres originating in the hindbrain dopaminergic neuron bands. The medium spiny neurons (MSNs) are interconnected via local collaterals of their axons projecting to other nuclei of the basal ganglia. The fast-spiking interneurons (FSIs) can form dendro-dendritic gap junctions between them; they may also be connected by standard axo-dendritic synapses. All these intra-striatal axo-dendritic connections () are GABAergic and hence inhibitory.
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pcbi-1001011-g001: The striatal GABAergic microcircuit studied in this paper.Primary input to the striatum comes from glutamatergic (GLU: ) fibres originating in the neocortex, thalamus, hippocampal formation and amygdala, and dopaminergic (DA: ▪) fibres originating in the hindbrain dopaminergic neuron bands. The medium spiny neurons (MSNs) are interconnected via local collaterals of their axons projecting to other nuclei of the basal ganglia. The fast-spiking interneurons (FSIs) can form dendro-dendritic gap junctions between them; they may also be connected by standard axo-dendritic synapses. All these intra-striatal axo-dendritic connections () are GABAergic and hence inhibitory.

Mentions: The striatal GABAergic microcircuit, shown in Figure 1, is formed by the connections between the GABAergic MSNs and FSIs. The MSNs are the only output neurons and comprise 90–97% of the neuron population in rat [19], [34], at a density of 84900 per [35]. The FSIs form 1–5% of the striatal neuron population [19], [36]. Stereological counting suggests that parvalbumin-immunoreactive neurons, the likely histochemical marker for FSIs [37], make up 0.7% of the striatum [38], [39]. As we will see, our model supports this lower estimate: only an FSI density of at most 1% resulted in numbers of FSI connections that are consistent with current data.


Reconstructing the three-dimensional GABAergic microcircuit of the striatum.

Humphries MD, Wood R, Gurney K - PLoS Comput. Biol. (2010)

The striatal GABAergic microcircuit studied in this paper.Primary input to the striatum comes from glutamatergic (GLU: ) fibres originating in the neocortex, thalamus, hippocampal formation and amygdala, and dopaminergic (DA: ▪) fibres originating in the hindbrain dopaminergic neuron bands. The medium spiny neurons (MSNs) are interconnected via local collaterals of their axons projecting to other nuclei of the basal ganglia. The fast-spiking interneurons (FSIs) can form dendro-dendritic gap junctions between them; they may also be connected by standard axo-dendritic synapses. All these intra-striatal axo-dendritic connections () are GABAergic and hence inhibitory.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2991252&req=5

pcbi-1001011-g001: The striatal GABAergic microcircuit studied in this paper.Primary input to the striatum comes from glutamatergic (GLU: ) fibres originating in the neocortex, thalamus, hippocampal formation and amygdala, and dopaminergic (DA: ▪) fibres originating in the hindbrain dopaminergic neuron bands. The medium spiny neurons (MSNs) are interconnected via local collaterals of their axons projecting to other nuclei of the basal ganglia. The fast-spiking interneurons (FSIs) can form dendro-dendritic gap junctions between them; they may also be connected by standard axo-dendritic synapses. All these intra-striatal axo-dendritic connections () are GABAergic and hence inhibitory.
Mentions: The striatal GABAergic microcircuit, shown in Figure 1, is formed by the connections between the GABAergic MSNs and FSIs. The MSNs are the only output neurons and comprise 90–97% of the neuron population in rat [19], [34], at a density of 84900 per [35]. The FSIs form 1–5% of the striatal neuron population [19], [36]. Stereological counting suggests that parvalbumin-immunoreactive neurons, the likely histochemical marker for FSIs [37], make up 0.7% of the striatum [38], [39]. As we will see, our model supports this lower estimate: only an FSI density of at most 1% resulted in numbers of FSI connections that are consistent with current data.

Bottom Line: From these, we found the probabilities of intersection between the neurites of two neurons given their inter-somatic distance, and used these to construct three-dimensional striatal networks.We show that both properties influence striatal dynamics: the most potent inhibition of a MSN arises from a region of striatum at the edge of its dendritic field; and the combination of local gap junction and distal synaptic networks between FSIs sets a robust input-output regime for the MSN population.Our models thus intimately link striatal micro-anatomy to its dynamics, providing a biologically grounded platform for further study.

View Article: PubMed Central - PubMed

Affiliation: Adaptive Behaviour Research Group, Department of Psychology, University of Sheffield, Sheffield, United Kingdom. m.d.humphries@shef.ac.uk

ABSTRACT
A system's wiring constrains its dynamics, yet modelling of neural structures often overlooks the specific networks formed by their neurons. We developed an approach for constructing anatomically realistic networks and reconstructed the GABAergic microcircuit formed by the medium spiny neurons (MSNs) and fast-spiking interneurons (FSIs) of the adult rat striatum. We grew dendrite and axon models for these neurons and extracted probabilities for the presence of these neurites as a function of distance from the soma. From these, we found the probabilities of intersection between the neurites of two neurons given their inter-somatic distance, and used these to construct three-dimensional striatal networks. The MSN dendrite models predicted that half of all dendritic spines are within 100µm of the soma. The constructed networks predict distributions of gap junctions between FSI dendrites, synaptic contacts between MSNs, and synaptic inputs from FSIs to MSNs that are consistent with current estimates. The models predict that to achieve this, FSIs should be at most 1% of the striatal population. They also show that the striatum is sparsely connected: FSI-MSN and MSN-MSN contacts respectively form 7% and 1.7% of all possible connections. The models predict two striking network properties: the dominant GABAergic input to a MSN arises from neurons with somas at the edge of its dendritic field; and FSIs are inter-connected on two different spatial scales: locally by gap junctions and distally by synapses. We show that both properties influence striatal dynamics: the most potent inhibition of a MSN arises from a region of striatum at the edge of its dendritic field; and the combination of local gap junction and distal synaptic networks between FSIs sets a robust input-output regime for the MSN population. Our models thus intimately link striatal micro-anatomy to its dynamics, providing a biologically grounded platform for further study.

Show MeSH
Related in: MedlinePlus