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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.


Identified PV+/Scgn- and PV+/Scgn+ interneurons in the dorsal striatum of rats have distinct electrophysiological properties.(A) The mean action potential waveforms of PV+/Scgn-(green) and PV+/Scgn+(blue) interneurons. Both groups had short waveforms (around 1 ms). Waveforms were split in to D1 (baseline to its peak) and D2 (return to the baseline from peak). The D1 segment of PV+/Scgn+interneurons was significantly shorter than that of PV+/Scgn- interneurons. (B) The median firing rates of the two populations of PV+ interneuron were similar during SWA, but PV+/Scgn+ interneurons had a significantly higher firing rate than PV+/Scgn- interneurons during cortical activation. (C–F) The similarity of firing patterns between pairs of PV+/Scgn-, PV+/Scgn+ and cholinergic (ChAT+) interneurons was assessed by calculating the correlation coefficient (Spearman) between interspike interval (ISI) histograms. (Ci–ii) ISI histograms from the spike trains for two cholinergic interneurons recorded separately during cortical activation. (Ciii) Scatter plot of the % count in each ISI bin for the two ChAT+ interneurons plotted against each other. Because of the similar (unimodal) ISI distributions, the Spearman Rho correlation coefficient (r) for the pair of ChAT+ interneurons is relatively high. (Di–ii) As in C, but the analysis is now performed on two separately recorded PV+ interneurons. (Diii) Because of the more variable ISI distributions, the correlation coefficient (r) is relatively low. (E) Histogram of the correlation coefficients of 276 cholinergic interneuron pairs from recordings during cortical activation. The majority of correlations are high, indicating similar ISI histograms across the population. (F) Histogram of the correlation coefficients of 325 PV+ interneuron pairs from recordings during cortical activation. Correlations strengths are relatively spread; indicating ISI histograms are less similar than those of the cholinergic population. (G, H) Comparison of Spearman correlation coefficients of all PV+/Scgn-, PV+/Scgn+ and ChAT+ interneuron pairs recorded in SWA (G) and cortical activation (H). In both brain states, the correlation coefficients between pairs of PV+/Scgn+ ISI histograms was significantly higher than that of PV+/Scgn- pairs, but not significantly different to ChAT+ interneuron pairs.DOI:http://dx.doi.org/10.7554/eLife.16088.01010.7554/eLife.16088.011Figure 5—source data 1.Source data for Figure 5A,B,G,H.DOI:http://dx.doi.org/10.7554/eLife.16088.011
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fig5: Identified PV+/Scgn- and PV+/Scgn+ interneurons in the dorsal striatum of rats have distinct electrophysiological properties.(A) The mean action potential waveforms of PV+/Scgn-(green) and PV+/Scgn+(blue) interneurons. Both groups had short waveforms (around 1 ms). Waveforms were split in to D1 (baseline to its peak) and D2 (return to the baseline from peak). The D1 segment of PV+/Scgn+interneurons was significantly shorter than that of PV+/Scgn- interneurons. (B) The median firing rates of the two populations of PV+ interneuron were similar during SWA, but PV+/Scgn+ interneurons had a significantly higher firing rate than PV+/Scgn- interneurons during cortical activation. (C–F) The similarity of firing patterns between pairs of PV+/Scgn-, PV+/Scgn+ and cholinergic (ChAT+) interneurons was assessed by calculating the correlation coefficient (Spearman) between interspike interval (ISI) histograms. (Ci–ii) ISI histograms from the spike trains for two cholinergic interneurons recorded separately during cortical activation. (Ciii) Scatter plot of the % count in each ISI bin for the two ChAT+ interneurons plotted against each other. Because of the similar (unimodal) ISI distributions, the Spearman Rho correlation coefficient (r) for the pair of ChAT+ interneurons is relatively high. (Di–ii) As in C, but the analysis is now performed on two separately recorded PV+ interneurons. (Diii) Because of the more variable ISI distributions, the correlation coefficient (r) is relatively low. (E) Histogram of the correlation coefficients of 276 cholinergic interneuron pairs from recordings during cortical activation. The majority of correlations are high, indicating similar ISI histograms across the population. (F) Histogram of the correlation coefficients of 325 PV+ interneuron pairs from recordings during cortical activation. Correlations strengths are relatively spread; indicating ISI histograms are less similar than those of the cholinergic population. (G, H) Comparison of Spearman correlation coefficients of all PV+/Scgn-, PV+/Scgn+ and ChAT+ interneuron pairs recorded in SWA (G) and cortical activation (H). In both brain states, the correlation coefficients between pairs of PV+/Scgn+ ISI histograms was significantly higher than that of PV+/Scgn- pairs, but not significantly different to ChAT+ interneuron pairs.DOI:http://dx.doi.org/10.7554/eLife.16088.01010.7554/eLife.16088.011Figure 5—source data 1.Source data for Figure 5A,B,G,H.DOI:http://dx.doi.org/10.7554/eLife.16088.011

Mentions: Striatal PV+ interneurons have short duration (<1 ms) action potentials (Mallet et al., 2005; Sharott et al., 2012), a characteristic often used to putatively identify them (as FSIs) in awake, behaving animals (Adler et al., 2013; Berke, 2004). In agreement with this, our recordings confirmed that the action potential waveforms of all PV+ interneurons, irrespective of Scgn immunoreactivity, were brief (1.09 ± 0.06 ms, n = 24; Figure 5A.). Further analysis showed that the duration of the first deflection (D1) of the action potentials (see Figure 5A) of PV+/Scgn+ interneurons (n = 10 cells; 0.31 ± 0.014 ms) was significantly shorter than those of PV+/Scgn- interneurons (n = 14 cells; 0.39 ± 0.02 ms) (Mann Whitney, p=0.006). Although the firing rates of PV+ interneurons as a whole could vary substantially (range: 0.01 – 22.52 spikes/s; see Figure 4) during SWA, the average firing rates of PV+/Scgn+ and PV+/Scgn- interneurons were similar in this brain state (Figure 5B, Figure 5—source data 1). However, during cortical activation, the firing rate of PV+/Scgn+interneurons (median = 13.8 spikes/s) was significantly higher than that of the PV+/Scgn- interneurons (median = 3.74 spikes/s, Mann-Whitney U test, p=0.03; Figure 5B, Figure 5—source data 1).10.7554/eLife.16088.010Figure 5.Identified PV+/Scgn- and PV+/Scgn+ interneurons in the dorsal striatum of rats have distinct electrophysiological properties.


Secretagogin expression delineates functionally-specialized populations of striatal parvalbumin-containing interneurons
Identified PV+/Scgn- and PV+/Scgn+ interneurons in the dorsal striatum of rats have distinct electrophysiological properties.(A) The mean action potential waveforms of PV+/Scgn-(green) and PV+/Scgn+(blue) interneurons. Both groups had short waveforms (around 1 ms). Waveforms were split in to D1 (baseline to its peak) and D2 (return to the baseline from peak). The D1 segment of PV+/Scgn+interneurons was significantly shorter than that of PV+/Scgn- interneurons. (B) The median firing rates of the two populations of PV+ interneuron were similar during SWA, but PV+/Scgn+ interneurons had a significantly higher firing rate than PV+/Scgn- interneurons during cortical activation. (C–F) The similarity of firing patterns between pairs of PV+/Scgn-, PV+/Scgn+ and cholinergic (ChAT+) interneurons was assessed by calculating the correlation coefficient (Spearman) between interspike interval (ISI) histograms. (Ci–ii) ISI histograms from the spike trains for two cholinergic interneurons recorded separately during cortical activation. (Ciii) Scatter plot of the % count in each ISI bin for the two ChAT+ interneurons plotted against each other. Because of the similar (unimodal) ISI distributions, the Spearman Rho correlation coefficient (r) for the pair of ChAT+ interneurons is relatively high. (Di–ii) As in C, but the analysis is now performed on two separately recorded PV+ interneurons. (Diii) Because of the more variable ISI distributions, the correlation coefficient (r) is relatively low. (E) Histogram of the correlation coefficients of 276 cholinergic interneuron pairs from recordings during cortical activation. The majority of correlations are high, indicating similar ISI histograms across the population. (F) Histogram of the correlation coefficients of 325 PV+ interneuron pairs from recordings during cortical activation. Correlations strengths are relatively spread; indicating ISI histograms are less similar than those of the cholinergic population. (G, H) Comparison of Spearman correlation coefficients of all PV+/Scgn-, PV+/Scgn+ and ChAT+ interneuron pairs recorded in SWA (G) and cortical activation (H). In both brain states, the correlation coefficients between pairs of PV+/Scgn+ ISI histograms was significantly higher than that of PV+/Scgn- pairs, but not significantly different to ChAT+ interneuron pairs.DOI:http://dx.doi.org/10.7554/eLife.16088.01010.7554/eLife.16088.011Figure 5—source data 1.Source data for Figure 5A,B,G,H.DOI:http://dx.doi.org/10.7554/eLife.16088.011
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fig5: Identified PV+/Scgn- and PV+/Scgn+ interneurons in the dorsal striatum of rats have distinct electrophysiological properties.(A) The mean action potential waveforms of PV+/Scgn-(green) and PV+/Scgn+(blue) interneurons. Both groups had short waveforms (around 1 ms). Waveforms were split in to D1 (baseline to its peak) and D2 (return to the baseline from peak). The D1 segment of PV+/Scgn+interneurons was significantly shorter than that of PV+/Scgn- interneurons. (B) The median firing rates of the two populations of PV+ interneuron were similar during SWA, but PV+/Scgn+ interneurons had a significantly higher firing rate than PV+/Scgn- interneurons during cortical activation. (C–F) The similarity of firing patterns between pairs of PV+/Scgn-, PV+/Scgn+ and cholinergic (ChAT+) interneurons was assessed by calculating the correlation coefficient (Spearman) between interspike interval (ISI) histograms. (Ci–ii) ISI histograms from the spike trains for two cholinergic interneurons recorded separately during cortical activation. (Ciii) Scatter plot of the % count in each ISI bin for the two ChAT+ interneurons plotted against each other. Because of the similar (unimodal) ISI distributions, the Spearman Rho correlation coefficient (r) for the pair of ChAT+ interneurons is relatively high. (Di–ii) As in C, but the analysis is now performed on two separately recorded PV+ interneurons. (Diii) Because of the more variable ISI distributions, the correlation coefficient (r) is relatively low. (E) Histogram of the correlation coefficients of 276 cholinergic interneuron pairs from recordings during cortical activation. The majority of correlations are high, indicating similar ISI histograms across the population. (F) Histogram of the correlation coefficients of 325 PV+ interneuron pairs from recordings during cortical activation. Correlations strengths are relatively spread; indicating ISI histograms are less similar than those of the cholinergic population. (G, H) Comparison of Spearman correlation coefficients of all PV+/Scgn-, PV+/Scgn+ and ChAT+ interneuron pairs recorded in SWA (G) and cortical activation (H). In both brain states, the correlation coefficients between pairs of PV+/Scgn+ ISI histograms was significantly higher than that of PV+/Scgn- pairs, but not significantly different to ChAT+ interneuron pairs.DOI:http://dx.doi.org/10.7554/eLife.16088.01010.7554/eLife.16088.011Figure 5—source data 1.Source data for Figure 5A,B,G,H.DOI:http://dx.doi.org/10.7554/eLife.16088.011
Mentions: Striatal PV+ interneurons have short duration (<1 ms) action potentials (Mallet et al., 2005; Sharott et al., 2012), a characteristic often used to putatively identify them (as FSIs) in awake, behaving animals (Adler et al., 2013; Berke, 2004). In agreement with this, our recordings confirmed that the action potential waveforms of all PV+ interneurons, irrespective of Scgn immunoreactivity, were brief (1.09 ± 0.06 ms, n = 24; Figure 5A.). Further analysis showed that the duration of the first deflection (D1) of the action potentials (see Figure 5A) of PV+/Scgn+ interneurons (n = 10 cells; 0.31 ± 0.014 ms) was significantly shorter than those of PV+/Scgn- interneurons (n = 14 cells; 0.39 ± 0.02 ms) (Mann Whitney, p=0.006). Although the firing rates of PV+ interneurons as a whole could vary substantially (range: 0.01 – 22.52 spikes/s; see Figure 4) during SWA, the average firing rates of PV+/Scgn+ and PV+/Scgn- interneurons were similar in this brain state (Figure 5B, Figure 5—source data 1). However, during cortical activation, the firing rate of PV+/Scgn+interneurons (median = 13.8 spikes/s) was significantly higher than that of the PV+/Scgn- interneurons (median = 3.74 spikes/s, Mann-Whitney U test, p=0.03; Figure 5B, Figure 5—source data 1).10.7554/eLife.16088.010Figure 5.Identified PV+/Scgn- and PV+/Scgn+ interneurons in the dorsal striatum of rats have distinct electrophysiological properties.

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 &lsquo;direct pathway&rsquo;, whereas PV+/Scgn- interneurons preferentially targeted &lsquo;indirect pathway&rsquo; 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.