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Secretagogin expression delineates functionally-specialized populations of striatal parvalbumin-containing interneurons

View Article: PubMed Central - PubMed

ABSTRACT

Corticostriatal afferents can engage parvalbumin-expressing (PV+) interneurons to rapidly curtail the activity of striatal projection neurons (SPNs), thus shaping striatal output. Schemes of basal ganglia circuit dynamics generally consider striatal PV+ interneurons to be homogenous, despite considerable heterogeneity in both form and function. We demonstrate that the selective co-expression of another calcium-binding protein, secretagogin (Scgn), separates PV+ interneurons in rat and primate striatum into two topographically-, physiologically- and structurally-distinct cell populations. In rats, these two interneuron populations differed in their firing rates, patterns and relationships with cortical oscillations in vivo. Moreover, the axons of identified PV+/Scgn+ interneurons preferentially targeted the somata of SPNs of the so-called ‘direct pathway’, whereas PV+/Scgn- interneurons preferentially targeted ‘indirect pathway’ SPNs. These two populations of interneurons could therefore provide a substrate through which either of the striatal output pathways can be rapidly and selectively inhibited to subsequently mediate the expression of behavioral routines.

Doi:: http://dx.doi.org/10.7554/eLife.16088.001

No MeSH data available.


Related in: MedlinePlus

PV+/Scgn- and PV+/Scgn+ interneurons differ in their temporal relationships with spiny projection neurons of the direct and indirect pathways.(Ai) Striatal projection neuron (SPN), juxtacellularly labelled with neurobiotin (NB) and identified by its densely spiny dendrites (top inset). This neuron’s soma does not express immunoreactvity for PPE (middle and bottom insets), identifying it as a direct pathway SPN (dSPN). (Aii) Two 10 s epochs of the inverted local field potential (iLFP) that were simultaneously recorded with single-unit activity in the striatum (all from same glass electrode). The identified dSPN tended to fire action potentials (yellow) just before and around the peaks of the iLFP. (Aiii) Histograms of iLFP amplitude (top) and dSPN spike firing (below), confirming that the dSPN fires most often before the center of the iLFP peak. (Bi) Juxtacellularly-labelled indirect pathway SPN (iSPN), identified by its somatic expression of PPE. (Bii, Biii) The iSPN tended to fire action potentials (magenta) just after and around the peaks of the iLFP (Bii), which is confirmed by the histograms of iLFP amplitude and spike firing (Biii). (C) Mean iLFP histograms and spike-firing probability histograms for all SPNs and all PV+ interneurons recorded (i), for identified dSPNs and iSPNs (ii), and for identified PV+/Scgn- and PV+/Scgn+ interneurons (iii). Note that, when considered as whole populations, SPNs and PV+ interneurons fire at similar times with respect to the iLFP, but also that firing times diverge when the SPN and PV+ interneuron populations are divided according to their dichotomous molecular identities. (D) The median firing times of all SPN and all PV+ interneurons are not significantly different (upper plot). When the subpopulations are analyzed (lower plots), dSPNs fire significantly earlier than iSPNs, and PV+/Scgn- interneurons fire significantly earlier that PV+/Scgn+ interneurons. Furthermore, PV+/Scgn- interneurons fire significantly earlier than iSPNs, but not dSPNs. Note also that PV+/Scgn+ interneurons fire significantly later than dSPNs (Kruskal Wallis ANOVA on rank [p=0.0006] with post-hoc Dunn tests). AU, arbitrary units. (Ai, Bi, Scale bars are 20 µM, except for those in dendrite images, which are 5 µM Aii, Bii, Vertical scale bars for unit activity and iLFPs are 1 mV; Horizontal scale bars are 1 s).DOI:http://dx.doi.org/10.7554/eLife.16088.01710.7554/eLife.16088.018Figure 9—source data 1.Source data for Figure 9C, D.DOI:http://dx.doi.org/10.7554/eLife.16088.018
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fig9: PV+/Scgn- and PV+/Scgn+ interneurons differ in their temporal relationships with spiny projection neurons of the direct and indirect pathways.(Ai) Striatal projection neuron (SPN), juxtacellularly labelled with neurobiotin (NB) and identified by its densely spiny dendrites (top inset). This neuron’s soma does not express immunoreactvity for PPE (middle and bottom insets), identifying it as a direct pathway SPN (dSPN). (Aii) Two 10 s epochs of the inverted local field potential (iLFP) that were simultaneously recorded with single-unit activity in the striatum (all from same glass electrode). The identified dSPN tended to fire action potentials (yellow) just before and around the peaks of the iLFP. (Aiii) Histograms of iLFP amplitude (top) and dSPN spike firing (below), confirming that the dSPN fires most often before the center of the iLFP peak. (Bi) Juxtacellularly-labelled indirect pathway SPN (iSPN), identified by its somatic expression of PPE. (Bii, Biii) The iSPN tended to fire action potentials (magenta) just after and around the peaks of the iLFP (Bii), which is confirmed by the histograms of iLFP amplitude and spike firing (Biii). (C) Mean iLFP histograms and spike-firing probability histograms for all SPNs and all PV+ interneurons recorded (i), for identified dSPNs and iSPNs (ii), and for identified PV+/Scgn- and PV+/Scgn+ interneurons (iii). Note that, when considered as whole populations, SPNs and PV+ interneurons fire at similar times with respect to the iLFP, but also that firing times diverge when the SPN and PV+ interneuron populations are divided according to their dichotomous molecular identities. (D) The median firing times of all SPN and all PV+ interneurons are not significantly different (upper plot). When the subpopulations are analyzed (lower plots), dSPNs fire significantly earlier than iSPNs, and PV+/Scgn- interneurons fire significantly earlier that PV+/Scgn+ interneurons. Furthermore, PV+/Scgn- interneurons fire significantly earlier than iSPNs, but not dSPNs. Note also that PV+/Scgn+ interneurons fire significantly later than dSPNs (Kruskal Wallis ANOVA on rank [p=0.0006] with post-hoc Dunn tests). AU, arbitrary units. (Ai, Bi, Scale bars are 20 µM, except for those in dendrite images, which are 5 µM Aii, Bii, Vertical scale bars for unit activity and iLFPs are 1 mV; Horizontal scale bars are 1 s).DOI:http://dx.doi.org/10.7554/eLife.16088.01710.7554/eLife.16088.018Figure 9—source data 1.Source data for Figure 9C, D.DOI:http://dx.doi.org/10.7554/eLife.16088.018

Mentions: To test these predictions, we compared the spike timing of identified SPNs (n = 48) and PV+ interneurons (n = 26) recorded in anesthetized rats during SWA (Figure 9). A subset of recorded and neurobiotin-labelled SPNs (n = 36 of 48) were tested for their expression of PPE, which led to the identification of 18 dSPNs (Figure 9Ai) and 18 iSPNs (Figure 9Bi). A subset of PV+ interneurons (n = 15 of 26) were tested for their co-expression of Scgn, which led to the identification of 8 PV+/Scgn- and 7 PV+/Scgn+ interneurons. As a common reference point for the temporal analysis of all striatal neuron firing, we used the peak of the slow oscillation (~1 Hz) present in the inverted striatal local field potential (iLFP) that was simultaneously recorded with the single-unit activity (Figure 9Aii,Bii). The slow oscillation in the iLFP is of particular relevance because it is a proxy signal for the cortically-driven synchronized 'up states' of many SPNs in the vicinity of the electrode (Goto and O'Donnell, 2001; Stern et al., 1998). For each striatal neuron, we calculated histograms of the spike times and iLFP amplitudes across the iLFP peak in 100 time bins, irrespective of the length of the individual cycle (Figure 9A–C); this normalization procedure ensured that the variable durations of the slow oscillation components (Nakamura et al., 2014) and thus, variable ‘peak lengths’, did not confound the analysis.10.7554/eLife.16088.017Figure 9.PV+/Scgn- and PV+/Scgn+ interneurons differ in their temporal relationships with spiny projection neurons of the direct and indirect pathways.


Secretagogin expression delineates functionally-specialized populations of striatal parvalbumin-containing interneurons
PV+/Scgn- and PV+/Scgn+ interneurons differ in their temporal relationships with spiny projection neurons of the direct and indirect pathways.(Ai) Striatal projection neuron (SPN), juxtacellularly labelled with neurobiotin (NB) and identified by its densely spiny dendrites (top inset). This neuron’s soma does not express immunoreactvity for PPE (middle and bottom insets), identifying it as a direct pathway SPN (dSPN). (Aii) Two 10 s epochs of the inverted local field potential (iLFP) that were simultaneously recorded with single-unit activity in the striatum (all from same glass electrode). The identified dSPN tended to fire action potentials (yellow) just before and around the peaks of the iLFP. (Aiii) Histograms of iLFP amplitude (top) and dSPN spike firing (below), confirming that the dSPN fires most often before the center of the iLFP peak. (Bi) Juxtacellularly-labelled indirect pathway SPN (iSPN), identified by its somatic expression of PPE. (Bii, Biii) The iSPN tended to fire action potentials (magenta) just after and around the peaks of the iLFP (Bii), which is confirmed by the histograms of iLFP amplitude and spike firing (Biii). (C) Mean iLFP histograms and spike-firing probability histograms for all SPNs and all PV+ interneurons recorded (i), for identified dSPNs and iSPNs (ii), and for identified PV+/Scgn- and PV+/Scgn+ interneurons (iii). Note that, when considered as whole populations, SPNs and PV+ interneurons fire at similar times with respect to the iLFP, but also that firing times diverge when the SPN and PV+ interneuron populations are divided according to their dichotomous molecular identities. (D) The median firing times of all SPN and all PV+ interneurons are not significantly different (upper plot). When the subpopulations are analyzed (lower plots), dSPNs fire significantly earlier than iSPNs, and PV+/Scgn- interneurons fire significantly earlier that PV+/Scgn+ interneurons. Furthermore, PV+/Scgn- interneurons fire significantly earlier than iSPNs, but not dSPNs. Note also that PV+/Scgn+ interneurons fire significantly later than dSPNs (Kruskal Wallis ANOVA on rank [p=0.0006] with post-hoc Dunn tests). AU, arbitrary units. (Ai, Bi, Scale bars are 20 µM, except for those in dendrite images, which are 5 µM Aii, Bii, Vertical scale bars for unit activity and iLFPs are 1 mV; Horizontal scale bars are 1 s).DOI:http://dx.doi.org/10.7554/eLife.16088.01710.7554/eLife.16088.018Figure 9—source data 1.Source data for Figure 9C, D.DOI:http://dx.doi.org/10.7554/eLife.16088.018
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fig9: PV+/Scgn- and PV+/Scgn+ interneurons differ in their temporal relationships with spiny projection neurons of the direct and indirect pathways.(Ai) Striatal projection neuron (SPN), juxtacellularly labelled with neurobiotin (NB) and identified by its densely spiny dendrites (top inset). This neuron’s soma does not express immunoreactvity for PPE (middle and bottom insets), identifying it as a direct pathway SPN (dSPN). (Aii) Two 10 s epochs of the inverted local field potential (iLFP) that were simultaneously recorded with single-unit activity in the striatum (all from same glass electrode). The identified dSPN tended to fire action potentials (yellow) just before and around the peaks of the iLFP. (Aiii) Histograms of iLFP amplitude (top) and dSPN spike firing (below), confirming that the dSPN fires most often before the center of the iLFP peak. (Bi) Juxtacellularly-labelled indirect pathway SPN (iSPN), identified by its somatic expression of PPE. (Bii, Biii) The iSPN tended to fire action potentials (magenta) just after and around the peaks of the iLFP (Bii), which is confirmed by the histograms of iLFP amplitude and spike firing (Biii). (C) Mean iLFP histograms and spike-firing probability histograms for all SPNs and all PV+ interneurons recorded (i), for identified dSPNs and iSPNs (ii), and for identified PV+/Scgn- and PV+/Scgn+ interneurons (iii). Note that, when considered as whole populations, SPNs and PV+ interneurons fire at similar times with respect to the iLFP, but also that firing times diverge when the SPN and PV+ interneuron populations are divided according to their dichotomous molecular identities. (D) The median firing times of all SPN and all PV+ interneurons are not significantly different (upper plot). When the subpopulations are analyzed (lower plots), dSPNs fire significantly earlier than iSPNs, and PV+/Scgn- interneurons fire significantly earlier that PV+/Scgn+ interneurons. Furthermore, PV+/Scgn- interneurons fire significantly earlier than iSPNs, but not dSPNs. Note also that PV+/Scgn+ interneurons fire significantly later than dSPNs (Kruskal Wallis ANOVA on rank [p=0.0006] with post-hoc Dunn tests). AU, arbitrary units. (Ai, Bi, Scale bars are 20 µM, except for those in dendrite images, which are 5 µM Aii, Bii, Vertical scale bars for unit activity and iLFPs are 1 mV; Horizontal scale bars are 1 s).DOI:http://dx.doi.org/10.7554/eLife.16088.01710.7554/eLife.16088.018Figure 9—source data 1.Source data for Figure 9C, D.DOI:http://dx.doi.org/10.7554/eLife.16088.018
Mentions: To test these predictions, we compared the spike timing of identified SPNs (n = 48) and PV+ interneurons (n = 26) recorded in anesthetized rats during SWA (Figure 9). A subset of recorded and neurobiotin-labelled SPNs (n = 36 of 48) were tested for their expression of PPE, which led to the identification of 18 dSPNs (Figure 9Ai) and 18 iSPNs (Figure 9Bi). A subset of PV+ interneurons (n = 15 of 26) were tested for their co-expression of Scgn, which led to the identification of 8 PV+/Scgn- and 7 PV+/Scgn+ interneurons. As a common reference point for the temporal analysis of all striatal neuron firing, we used the peak of the slow oscillation (~1 Hz) present in the inverted striatal local field potential (iLFP) that was simultaneously recorded with the single-unit activity (Figure 9Aii,Bii). The slow oscillation in the iLFP is of particular relevance because it is a proxy signal for the cortically-driven synchronized 'up states' of many SPNs in the vicinity of the electrode (Goto and O'Donnell, 2001; Stern et al., 1998). For each striatal neuron, we calculated histograms of the spike times and iLFP amplitudes across the iLFP peak in 100 time bins, irrespective of the length of the individual cycle (Figure 9A–C); this normalization procedure ensured that the variable durations of the slow oscillation components (Nakamura et al., 2014) and thus, variable ‘peak lengths’, did not confound the analysis.10.7554/eLife.16088.017Figure 9.PV+/Scgn- and PV+/Scgn+ interneurons differ in their temporal relationships with spiny projection neurons of the direct and indirect pathways.

View Article: PubMed Central - PubMed

ABSTRACT

Corticostriatal afferents can engage parvalbumin-expressing (PV+) interneurons to rapidly curtail the activity of striatal projection neurons (SPNs), thus shaping striatal output. Schemes of basal ganglia circuit dynamics generally consider striatal PV+ interneurons to be homogenous, despite considerable heterogeneity in both form and function. We demonstrate that the selective co-expression of another calcium-binding protein, secretagogin (Scgn), separates PV+ interneurons in rat and primate striatum into two topographically-, physiologically- and structurally-distinct cell populations. In rats, these two interneuron populations differed in their firing rates, patterns and relationships with cortical oscillations in vivo. Moreover, the axons of identified PV+/Scgn+ interneurons preferentially targeted the somata of SPNs of the so-called ‘direct pathway’, whereas PV+/Scgn- interneurons preferentially targeted ‘indirect pathway’ SPNs. These two populations of interneurons could therefore provide a substrate through which either of the striatal output pathways can be rapidly and selectively inhibited to subsequently mediate the expression of behavioral routines.

Doi:: http://dx.doi.org/10.7554/eLife.16088.001

No MeSH data available.


Related in: MedlinePlus