Contribution of different classes of glutamate receptors in the corticostriatal polysynaptic responses from striatal direct and indirect projection neurons

Abstract

BackgroundPrevious work showed differences in the polysynaptic activation of GABAergic synapses during corticostriatal suprathreshold responses in direct and indirect striatal projection neurons (dSPNs and iSPNs). Here, we now show differences and similarities in the polysynaptic activation of cortical glutamatergic synapses on the same responses. Corticostriatal contacts have been extensively studied. However, several questions remain unanswered, e.g.: what are the differences and similarities in the responses to glutamate in dSPNs and iSPNs? Does glutamatergic synaptic activation exhibits a distribution of latencies over time in vitro? That would be a strong suggestion of polysynaptic cortical convergence. What is the role of kainate receptors in corticostriatal transmission? Current-clamp recordings were used to answer these questions. One hypothesis was: if prolonged synaptic activation distributed along time was present, then it would be mainly generated from the cortex, and not from the striatum.ResultsBy isolating responses from AMPA-receptors out of the complex suprathreshold response of SPNs, it is shown that a single cortical stimulus induces early and late synaptic activation lasting hundreds of milliseconds. Prolonged responses depended on cortical stimulation because they could not be elicited using intrastriatal stimulation, even if GABAergic transmission was blocked. Thus, the results are not explained by differences in evoked inhibition. Moreover, inhibitory participation was larger after cortical than after intrastriatal stimulation. A strong activation of interneurons was obtained from the cortex, demonstrating that polysynaptic activation includes the striatum. Prolonged kainate (KA) receptor responses were also elicited from the cortex. Responses of dSPNs and iSPNs did not depend on the cortical area stimulated. In contrast to AMPA-receptors, responses from NMDA- and KA-receptors do not exhibit early and late responses, but generate slow responses that contribute to plateau depolarizations.ConclusionsAs it has been established in previous physiological studies in vivo, synaptic invasion over different latencies, spanning hundreds of milliseconds after a single stimulus strongly indicates convergent polysynaptic activation. Interconnected cortical neurons converging on the same SPNs may explain prolonged corticostriatal responses. Glutamate receptors participation in these responses is described as well as differences and similarities between dSPNs and iSPNs.

Complete Disruption of the Kainate Receptor Gene Family Results in Corticostriatal Dysfunction in Mice

“…Unlike AMPA receptors, localization of kainate receptors to postsynaptic densities is not ubiquitous in all neurons throughout the CNS. Prior studies have found that there is a slow synaptic current in SPNs that was not inhibited by AMPA and NMDA receptor antagonism (Chergui et al, 2000) but which was reduced by the relatively selective kainate receptor blocker ACET (Vizcarra-Chacon et al, 2013). We confirmed that kainate receptors contribute to corticostriatal synaptic transmission by mediating a small amplitude GYKI53655-resistant current that was partially blocked by the non-selective AMPA/kainate receptor antagonist CNQX (n = 20 WT, n = 3 5ko) (Figure 3B & C).…”

“…The mice also had multiple alterations in motor behaviors with a classic hind limb clasping phenotype, impairments in the accelerating rotarod, and alterations in gait. Kainate receptors are expressed in striatal neurons, yet little is known about their contribution to synaptic transmission (Chergui et al, 2000; Vizcarra-Chacon et al, 2013). We found that corticostriatal synaptic transmission in the dorsal striatum was impaired, with changes in the NMDA:AMPA ratio, as well as reductions in the field potential response and lower mEPSC frequencies both suggesting the existence of fewer excitatory synapses.…”

Duration differences of corticostriatal responses in striatal projection neurons depend on calcium activated potassium currents

“…Near synaptic sites of SPNs, NMDA, Ca V 1, Ca V 2.3, and Ca V 3 channels become a main source of Ca 2+ (Galarraga et al, 1997; Carter and Sabatini, 2004; Higley and Sabatini, 2008; Flores-Barrera et al, 2011). Because Ca 2+ -activated K + -channels could be present in the synaptic regions of dendrites (Ngo-Anh et al, 2005; Gu et al, 2008; Benhassine and Berger, 2009; Wynne et al, 2009; Faber, 2010; Grewe et al, 2010; Allen et al, 2011; Hosy et al, 2011; Tonini et al, 2013, e.g., Womack et al, 2004), one question to ask is whether Ca 2+ -activated K + currents are involved in dendritic synaptic integration and the repolarization of polysynaptic corticostriatal responses (Vizcarra-Chacon et al, 2013), given that Ca 2+ sources could be different than in the soma. Different sources of Ca 2+ to activate Ca 2+ -dependent K + -currents in the dendrites and the soma-axon hillock regions could imply that synaptic inputs and the generation of action potentials may be regulated differentially.…”

KV7 Channels Regulate Firing during Synaptic Integration in GABAergic Striatal Neurons

“…It has been shown that cholinergic neurons respond with a slightly briefer latency than the responses of SPNs [1, 24]. In addition, continuous firing of cholinergic interneurons maintains a tonic level of ACh in the striatum [7, 24, 45], muscarinic M 1 receptors are expressed in all SPNs, and K V 7 channels have been shown to compose a minor but functionally important part of the intrinsic voltage gated currents that are present in all SPNs [34].…”