[Abstract Title]. - Society for Neuroscience

Topic: B.11.a. Synapses
Support: INSERM
Title: Impact of neurotransmitters uptake by astrocytes on corticostriatal information processing
Authors: *L. VENANCE 1 , V. GOUBARD 2 , J.-M. DENIAU 3 ;
1 Dynamique et Physiopathol des Reseaux Neuronaux, INSERM U-667, Col. de France, Paris,
France; 2 INSERM U667, College de France, France; 3 INSERM U667, College de france, France
Abstract: Basal ganglia, an ensemble of sub-cortical interconnected nuclei, are involved in
learning of contextual cognitivo-motor sequences related to environmental stimuli. Striatum, the
main input nucleus of basal ganglia, receives glutamatergic inputs from the whole cerebral
cortex. The striatal output neurons (medium-sized spiny neurons, MSNs), the main neuronal
striatal population, act as detectors and integrators of distributed patterns of cortical activity.
Modulation of release and uptake of neurotransmitters constitutes a key step in the information
processing. Astrocytes play a predominant role in the uptake of neurotransmitters. However, the
impact of astrocytes on corticostriatal transmission and synaptic plasticity remains to be
determined. For this purpose, we have used rat brain slices in which connections between
cortical pyramidal cells and MSNs were preserved. We performed electrical stimulation in layer
V of the somatosensory cortex while recording MSNs and astrocytes by double patch-clamp in
the dorsal striatum. Cortical stimulations evoked reliable glutamatergic excitatory postsynaptic
currents (EPSCs) in MSNs and efficient inward currents in astrocytes. Such astrocytic evokedcurrents
displayed latency of 4.74±0.32 ms, amplitude of 55.4±7.0 pA and rise time of 11.9±0.8
ms (n=29). Astrocytic evoked-currents originated mainly from the activities of glutamate and
GABA transporters. Indeed, dihydrokainic acid (300 mM; an inhibitor of glutamate transporter-
1) and nipecotic acid (500 mM; a non-specific GABA transporter inhibitor) inhibited cortically
astrocytic evoked-currents by 30.3±7.5 % and 29.2±5.5 % (n=12 and n=10) respectively, and
47.8±6.0 % (n=5) when applied together. Inhibition of glutamate and GABA transporters led to
significant decreases of the cortically MSN-evoked responses: 20.2±7.5 % (n=8) and 41.7±12.7
% (n=5), respectively. We have determined the characteristics of short-term plasticity in MSNs
and astrocytes. Namely, we have observed some facilitation and depression of the MSN EPSCs
as well as astrocytic transporter currents, depending on the paired-pulses intervals. Finally, we
have observed that magnitudes of facilitation and depression of cortically-evoked EPSCs were
mainly increased after glutamate and GABA uptakes inhibitions.
In conclusion, our experiments indicate that neurotransmitters uptake by astrocytes is particularly
efficient in the corticostriatal axis and have a strong impact on transmission and synaptic
plasticity. Such astrocytic properties could play a determinant role in the MSN coincidence
detection of cortical activities.
Disclosures: L. Venance , None; V. Goubard, None; J. Deniau, None.
Poster