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

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.

Input- and Cell-Type-Specific Endocannabinoid-Dependent LTD in the Striatum

“…Finally, this LTD was blocked by NMDAR antagonist (R-CPP 10 μM) (Figure 5K, 95 ± 7 % of baseline, n = 5; p =0.44, Wilcoxon), indicating that LTD induced by oSTDP paradigm at thalamostriatal synapses is NMDAR-dependent rather than eCB-dependent. This finding, together with a recent report (Ellender et al, 2013), suggest that thalamostriatal synapses express a different form of LTD that does not involve CB1R activation.…”

“…It is interesting that the oSTDP protocol could induce an NMDAR-dependent LTD that is insensitive to eCB. It has been shown that thalamostriatal inputs from Pf exhibit NMDAR-dependent LTD, regardless of using ‘pre-post’ or ‘post-pre’ STDP induction protocols (Ellender et al, 2013). This could imply that when salient stimuli emerge with background stimulation, attentional shift mediated by thalamostriatal system wanes.…”

Pathway-Specific Remodeling of Thalamostriatal Synapses in Parkinsonian Mice

“…Our data indicate that reduced thalamostriatal synaptic input is specific to dMSNs in parkinsonian animals. Although our study did not selectively target Pf, other work has found distinct synaptic properties at Pf vs. central lateral thalamic inputs (Ellender et al, 2013), indicating that it will be critical to learn whether changes to thalamostriatal inputs in parkinsonian animals apply only to specific intralaminar nuclei or more broadly.…”

Striatal synapses, circuits, and Parkinson's disease

“…These mechanisms may be absent at axoshaft PF synapses. Perhaps to compensate for this anatomical feature, PF synapses have a robust complement of NMDAR-type glutamate receptors [78]. The significance of these unique properties of PF synapses is unclear but could be related to the poly-sensory, alerting nature of the information relayed by PF [79].…”