• Open Access

Heterogeneous properties of central lateral and parafascicular thalamic synapses in the striatum

Authors


  • J. Harwood and P. Kosillo contributed equally.

T. J. Ellender: MRC Anatomical Neuropharmacology Unit, Department of Pharmacology, Mansfield Road, Oxford OX1 3TH, UK.  Email: tommas.ellender@pharm.ox.ac.uk

Key points

  • • The excitatory afferents to the striatum from the cortex and thalamus are critical in the expression of basal ganglia function.
  • • Thalamostriatal afferents are markedly heterogeneous and arise in different subnuclei of the intralaminar thalamus.
  • • We used an optogenetic approach, to isolate and selectively activate thalamostriatal afferents arising in the central lateral or parafascicular thalamic nuclei, and to study the properties of their synapses with principal striatal neurons, the medium-spiny neurons.
  • • Thalamostriatal synapses differ in many aspects and our data suggest that inputs from the central lateral nucleus are efficient drivers of medium-spiny neuron action potential firing, whereas inputs from the parafascicular nucleus are likely to be modulatory.
  • • These results suggest distinct roles for thalamostriatal inputs from different subnuclei of the thalamus and will help us understand how the striatal circuit operates in health and disease.

Abstract  To understand the principles of operation of the striatum it is critical to elucidate the properties of the main excitatory inputs from cortex and thalamus, as well as their ability to activate the main neurons of the striatum, the medium spiny neurons (MSNs). As the thalamostriatal projection is heterogeneous, we set out to isolate and study the thalamic afferent inputs to MSNs using small localized injections of adeno-associated virus carrying fusion genes for channelrhodopsin-2 and YFP, in either the rostral or caudal regions of the intralaminar thalamic nuclei (i.e. the central lateral or parafascicular nucleus). This enabled optical activation of specific thalamic afferents combined with whole-cell, patch-clamp recordings of MSNs and electrical stimulation of cortical afferents, in adult mice. We found that thalamostriatal synapses differ significantly in their peak amplitude responses, short-term dynamics and expression of ionotropic glutamate receptor subtypes. Our results suggest that central lateral synapses are most efficient in driving MSNs to depolarization, particularly those of the direct pathway, as they exhibit large amplitude responses, short-term facilitation and predominantly express postsynaptic AMPA receptors. In contrast, parafascicular synapses exhibit small amplitude responses, short-term depression and predominantly express postsynaptic NMDA receptors, suggesting a modulatory role, e.g. facilitating Ca2+-dependent processes. Indeed, pairing parafascicular, but not central lateral, presynaptic stimulation with action potentials in MSNs, leads to NMDA receptor- and Ca2+-dependent long-term depression at these synapses. We conclude that the main excitatory thalamostriatal afferents differ in many of their characteristics and suggest that they each contribute differentially to striatal information processing.

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