Different Corticostriatal Integration in Spiny Projection Neurons from Direct and Indirect Pathways

División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México México City, México.
Frontiers in Systems Neuroscience 06/2010; 4:15. DOI: 10.3389/fnsys.2010.00015
Source: PubMed


The striatum is the principal input structure of the basal ganglia. Major glutamatergic afferents to the striatum come from the cerebral cortex and make monosynaptic contacts with medium spiny projection neurons (MSNs) and interneurons. Also: glutamatergic afferents to the striatum come from the thalamus. Despite differences in axonal projections, dopamine (DA) receptors expression and differences in excitability between MSNs from "direct" and "indirect" basal ganglia pathways, these neuronal classes have been thought as electrophysiologically very similar. Based on work with bacterial artificial chromosome (BAC) transgenic mice, here it is shown that corticostriatal responses in D(1)- and D(2)-receptor expressing MSNs (D(1)- and D(2)-MSNs) are radically different so as to establish an electrophysiological footprint that readily differentiates between them. Experiments in BAC mice allowed us to predict, with high probability (P > 0.9), in rats or non-BAC mice, whether a recorded neuron, from rat or mouse, was going to be substance P or enkephalin (ENK) immunoreactive. Responses are more prolonged and evoke more action potentials in D(1)-MSNs, while they are briefer and exhibit intrinsic autoregenerative responses in D(2)-MSNs. A main cause for these differences was the interaction of intrinsic properties with the inhibitory contribution in each response. Inhibition always depressed corticostriatal depolarization in D(2)-MSNs, while it helped in sustaining prolonged depolarizations in D(1)-MSNs, in spite of depressing early discharge. Corticostriatal responses changed dramatically after striatal DA depletion in 6-hydroxy-dopamine (6-OHDA) lesioned animals: a response reduction was seen in substance P (SP)+ MSNs whereas an enhanced response was seen in ENK+ MSNs. The end result was that differences in the responses were greatly diminished after DA depletion.

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    • "Internal solution was (in mM): 120 KMeSO4, 2 MgCl2, 10 HEPES, 10 EGTA, 1 CaCl2, 0.2 Na2ATP, 0.2 Na3GTP, and 1% biocytin. Some recordings were carried out using sharp microelectrodes (80–120 MΩ) filled with 1% biocytin and 3M potassium acetate fabricated from borosilicate-glass (Flores-Barrera et al., 2010). Slices were superfused with CSF at 2 ml/min (34–36°C). "
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    ABSTRACT: The firing of striatal projection neurons (SPNs) exhibits afterhyperpolarizing potentials (AHPs) that determine discharge frequency. They are in part generated by Ca(2+)-activated K(+)-currents involving BK and SK components. It has previously been shown that suprathreshold corticostriatal responses are more prolonged and evoke more action potentials in direct pathway SPNs (dSPNs) than in indirect pathway SPNs (iSPNs). In contrast, iSPNs generate dendritic autoregenerative responses. Using whole cell recordings in brain slices, we asked whether the participation of Ca(2+)-activated K(+)-currents plays a role in these responses. Secondly, we asked if these currents may explain some differences in synaptic integration between dSPNs and iSPNs. Neurons obtained from BAC D1 and D2 GFP mice were recorded. We used charybdotoxin and apamin to block BK and SK channels, respectively. Both antagonists increased the depolarization and delayed the repolarization of suprathreshold corticostriatal responses in both neuron classes. We also used NS 1619 and NS 309 (CyPPA), to enhance BK and SK channels, respectively. Current enhancers hyperpolarized and accelerated the repolarization of corticostriatal responses in both neuron classes. Nevertheless, these drugs made evident that the contribution of Ca(2+)-activated K(+)-currents was different in dSPNs as compared to iSPNs: in dSPNs their activation was slower as though calcium took a diffusion delay to activate them. In contrast, their activation was fast and then sustained in iSPNs as though calcium flux activates them at the moment of entry. The blockade of Ca(2+)-activated K(+)-currents made iSPNs to look as dSPNs. Conversely, their enhancement made dSPNs to look as iSPNs. It is concluded that Ca(2+)-activated K(+)-currents are a main intrinsic determinant causing the differences in synaptic integration between corticostriatal polysynaptic responses between dSPNs and iSPNs.
    Full-text · Article · Oct 2013 · Frontiers in Systems Neuroscience
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    • "The similarities between dSPNs and iSPNs responses are that in both cases late responses last enough to be considered polysynaptic and contribute to about half the complex corticostriatal responses. A difference between dSPNs and iSPNs corticostriatal responses is that average areas under iSPNs responses are significantly smaller than those under dSPNs (P < 0.001; cf. Figure 2C and H) [25]. "
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    ABSTRACT: Background Previous 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. Results By 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. Conclusions As 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.
    Full-text · Article · Jun 2013 · BMC Neuroscience
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    • "The time window for synchronization is the up-state and the product of the ensemble is the same up-state shared by the neurons of the ensemble. Most probably, neurons sharing up-states do in fact maintain these plateau potentials along time due to their strong interconnections (Flores-Barrera et al., 2010). 6. Microcircuit dynamics as sequences of network states "

    Full-text · Chapter · Feb 2012
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