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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 have different biases in their distributions in the dorsal striatum of the rat.(A) Typical distributions of PV+/Scgn- interneurons (Ai) and PV+/Scgn+ interneurons (Aii) across 13 coronal planes encompassing the dorsal striatum in rat, with each dot representing a single neuron. (B) Densities of PV+/Scgn+ and PV+/Scgn- interneurons along the rostro-caudal axis of striatum. Note the increase in density of PV+/Scgn+ interneurons, and the small decrease in density of PV+/Scgn- interneurons, from rostral to caudal striatum. C,D Medio-lateral (C) and dorso-ventral (D) distributions of PV+/Scgn- interneurons (green line) and PV+/Scgn+ interneurons (blue line) along the 13 coronal planes. The presence of the asterisk (*) indicates a distribution that is significantly biased in one direction along the specified axis. Squares (□) indicate a significant difference in the distribution of the two populations of PV+ interneurons along the specified axis within a given coronal plane. Data are means of the normalized positions of allneurons counted ± SEMs. (E–G) Mean normalized medio-lateral (ML) and dorso-ventral (DV) positions of all PV+ (E), PV+/Scgn+ (F) and PV+/Scgn- (G) interneurons in each of 13 coronal planes (with respect to Bregma) of rat dorsal striatum. Grey circles on the end panels show the distribution of the mean values in each dimension. Note that clear biases in ML positions of all PV+ interneurons are similar to those of PV+/Scgn+ interneurons, whereas PV+/Scgn- interneurons are not clearly biased. (H) Mean normalized medio-lateral and dorso-ventral co-ordinates of all PV+ interneurons in each of 9 coronal planes of mouse dorsal striatum. Note that their positions are not clearly biased. (I, J) The difference in mean medio-lateral positions (I), but not dorso-ventral positions (J), between coronal planes of all rat PV+ interneurons is significantly higher than that of rat PV+/Scgn- interneurons and all PV+ interneurons in the mouse (Kruskal-Wallis ANOVA on ranks with post-hoc Dunn tests).DOI:http://dx.doi.org/10.7554/eLife.16088.00510.7554/eLife.16088.006Figure 2—source data 1.Source data for Figures 2 B–H.DOI:http://dx.doi.org/10.7554/eLife.16088.006
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fig2: PV+/Scgn+ and PV+/Scgn- interneurons have different biases in their distributions in the dorsal striatum of the rat.(A) Typical distributions of PV+/Scgn- interneurons (Ai) and PV+/Scgn+ interneurons (Aii) across 13 coronal planes encompassing the dorsal striatum in rat, with each dot representing a single neuron. (B) Densities of PV+/Scgn+ and PV+/Scgn- interneurons along the rostro-caudal axis of striatum. Note the increase in density of PV+/Scgn+ interneurons, and the small decrease in density of PV+/Scgn- interneurons, from rostral to caudal striatum. C,D Medio-lateral (C) and dorso-ventral (D) distributions of PV+/Scgn- interneurons (green line) and PV+/Scgn+ interneurons (blue line) along the 13 coronal planes. The presence of the asterisk (*) indicates a distribution that is significantly biased in one direction along the specified axis. Squares (□) indicate a significant difference in the distribution of the two populations of PV+ interneurons along the specified axis within a given coronal plane. Data are means of the normalized positions of allneurons counted ± SEMs. (E–G) Mean normalized medio-lateral (ML) and dorso-ventral (DV) positions of all PV+ (E), PV+/Scgn+ (F) and PV+/Scgn- (G) interneurons in each of 13 coronal planes (with respect to Bregma) of rat dorsal striatum. Grey circles on the end panels show the distribution of the mean values in each dimension. Note that clear biases in ML positions of all PV+ interneurons are similar to those of PV+/Scgn+ interneurons, whereas PV+/Scgn- interneurons are not clearly biased. (H) Mean normalized medio-lateral and dorso-ventral co-ordinates of all PV+ interneurons in each of 9 coronal planes of mouse dorsal striatum. Note that their positions are not clearly biased. (I, J) The difference in mean medio-lateral positions (I), but not dorso-ventral positions (J), between coronal planes of all rat PV+ interneurons is significantly higher than that of rat PV+/Scgn- interneurons and all PV+ interneurons in the mouse (Kruskal-Wallis ANOVA on ranks with post-hoc Dunn tests).DOI:http://dx.doi.org/10.7554/eLife.16088.00510.7554/eLife.16088.006Figure 2—source data 1.Source data for Figures 2 B–H.DOI:http://dx.doi.org/10.7554/eLife.16088.006

Mentions: Striatal afferents (and efferents) are topographically organized (Mailly et al., 2013; McGeorge and Faull, 1989). Thus, if a given cell population has a biased spatial distribution across striatum, it will likely receive privileged inputs from a specific subset of all striatal afferents. With this in mind, we next tested whether the two molecularly-distinct populations of PV+ interneuron, i.e. those that co-expressed Scgn (PV+/Scgn+) and those that did not (PV+/Scgn-), were preferentially localized to discrete striatal regions in the rat. The density of PV+/Scgn- interneurons remained relatively constant along the rostro-caudal axis of dorsal striatum, at least until the most caudal aspects where density decreased by around 75% (Figure 2Ai,B, Figure 2—source data 2). However, PV+/Scgn+ interneurons displayed a strikingly different pattern of localization, being more sparsely distributed across most striatal levels, except in the most caudal aspects where their density was around three times higher than that of PV+/Scgn- interneurons in any other plane (Figure 2Aii,B, Figure 2—source data 1). The two populations of interneurons were also differentially distributed along the medio-lateral axis of the striatum; PV+/Scgn- neurons were evenly distributed, whereas PV+/Scgn+ interneurons tended to distribute more laterally in the rostral striatum but more medially in caudal striatum (Figure 2C, Supplementary file 1, Figure 2—source data 1). This particular pattern of bias in the distribution of PV+/Scgn+ interneurons is highly unusual in that it has not been described for any other striatal cell population. Along the dorso-ventral axis, PV+/Scgn- interneurons were more likely than PV+/Scgn+ interneurons to display a slight dorsal bias in their localization (Figure 2D, Supplementary file 1, Figure 2—source data 1). Taken together, these data show that the selective expression of Scgn distinguishes two populations of PV+ interneurons that display significantly different spatial distributions in the dorsal striatum of the rat.10.7554/eLife.16088.005Figure 2.PV+/Scgn+ and PV+/Scgn- interneurons have different biases in their distributions in the dorsal striatum of the rat.


Secretagogin expression delineates functionally-specialized populations of striatal parvalbumin-containing interneurons
PV+/Scgn+ and PV+/Scgn- interneurons have different biases in their distributions in the dorsal striatum of the rat.(A) Typical distributions of PV+/Scgn- interneurons (Ai) and PV+/Scgn+ interneurons (Aii) across 13 coronal planes encompassing the dorsal striatum in rat, with each dot representing a single neuron. (B) Densities of PV+/Scgn+ and PV+/Scgn- interneurons along the rostro-caudal axis of striatum. Note the increase in density of PV+/Scgn+ interneurons, and the small decrease in density of PV+/Scgn- interneurons, from rostral to caudal striatum. C,D Medio-lateral (C) and dorso-ventral (D) distributions of PV+/Scgn- interneurons (green line) and PV+/Scgn+ interneurons (blue line) along the 13 coronal planes. The presence of the asterisk (*) indicates a distribution that is significantly biased in one direction along the specified axis. Squares (□) indicate a significant difference in the distribution of the two populations of PV+ interneurons along the specified axis within a given coronal plane. Data are means of the normalized positions of allneurons counted ± SEMs. (E–G) Mean normalized medio-lateral (ML) and dorso-ventral (DV) positions of all PV+ (E), PV+/Scgn+ (F) and PV+/Scgn- (G) interneurons in each of 13 coronal planes (with respect to Bregma) of rat dorsal striatum. Grey circles on the end panels show the distribution of the mean values in each dimension. Note that clear biases in ML positions of all PV+ interneurons are similar to those of PV+/Scgn+ interneurons, whereas PV+/Scgn- interneurons are not clearly biased. (H) Mean normalized medio-lateral and dorso-ventral co-ordinates of all PV+ interneurons in each of 9 coronal planes of mouse dorsal striatum. Note that their positions are not clearly biased. (I, J) The difference in mean medio-lateral positions (I), but not dorso-ventral positions (J), between coronal planes of all rat PV+ interneurons is significantly higher than that of rat PV+/Scgn- interneurons and all PV+ interneurons in the mouse (Kruskal-Wallis ANOVA on ranks with post-hoc Dunn tests).DOI:http://dx.doi.org/10.7554/eLife.16088.00510.7554/eLife.16088.006Figure 2—source data 1.Source data for Figures 2 B–H.DOI:http://dx.doi.org/10.7554/eLife.16088.006
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fig2: PV+/Scgn+ and PV+/Scgn- interneurons have different biases in their distributions in the dorsal striatum of the rat.(A) Typical distributions of PV+/Scgn- interneurons (Ai) and PV+/Scgn+ interneurons (Aii) across 13 coronal planes encompassing the dorsal striatum in rat, with each dot representing a single neuron. (B) Densities of PV+/Scgn+ and PV+/Scgn- interneurons along the rostro-caudal axis of striatum. Note the increase in density of PV+/Scgn+ interneurons, and the small decrease in density of PV+/Scgn- interneurons, from rostral to caudal striatum. C,D Medio-lateral (C) and dorso-ventral (D) distributions of PV+/Scgn- interneurons (green line) and PV+/Scgn+ interneurons (blue line) along the 13 coronal planes. The presence of the asterisk (*) indicates a distribution that is significantly biased in one direction along the specified axis. Squares (□) indicate a significant difference in the distribution of the two populations of PV+ interneurons along the specified axis within a given coronal plane. Data are means of the normalized positions of allneurons counted ± SEMs. (E–G) Mean normalized medio-lateral (ML) and dorso-ventral (DV) positions of all PV+ (E), PV+/Scgn+ (F) and PV+/Scgn- (G) interneurons in each of 13 coronal planes (with respect to Bregma) of rat dorsal striatum. Grey circles on the end panels show the distribution of the mean values in each dimension. Note that clear biases in ML positions of all PV+ interneurons are similar to those of PV+/Scgn+ interneurons, whereas PV+/Scgn- interneurons are not clearly biased. (H) Mean normalized medio-lateral and dorso-ventral co-ordinates of all PV+ interneurons in each of 9 coronal planes of mouse dorsal striatum. Note that their positions are not clearly biased. (I, J) The difference in mean medio-lateral positions (I), but not dorso-ventral positions (J), between coronal planes of all rat PV+ interneurons is significantly higher than that of rat PV+/Scgn- interneurons and all PV+ interneurons in the mouse (Kruskal-Wallis ANOVA on ranks with post-hoc Dunn tests).DOI:http://dx.doi.org/10.7554/eLife.16088.00510.7554/eLife.16088.006Figure 2—source data 1.Source data for Figures 2 B–H.DOI:http://dx.doi.org/10.7554/eLife.16088.006
Mentions: Striatal afferents (and efferents) are topographically organized (Mailly et al., 2013; McGeorge and Faull, 1989). Thus, if a given cell population has a biased spatial distribution across striatum, it will likely receive privileged inputs from a specific subset of all striatal afferents. With this in mind, we next tested whether the two molecularly-distinct populations of PV+ interneuron, i.e. those that co-expressed Scgn (PV+/Scgn+) and those that did not (PV+/Scgn-), were preferentially localized to discrete striatal regions in the rat. The density of PV+/Scgn- interneurons remained relatively constant along the rostro-caudal axis of dorsal striatum, at least until the most caudal aspects where density decreased by around 75% (Figure 2Ai,B, Figure 2—source data 2). However, PV+/Scgn+ interneurons displayed a strikingly different pattern of localization, being more sparsely distributed across most striatal levels, except in the most caudal aspects where their density was around three times higher than that of PV+/Scgn- interneurons in any other plane (Figure 2Aii,B, Figure 2—source data 1). The two populations of interneurons were also differentially distributed along the medio-lateral axis of the striatum; PV+/Scgn- neurons were evenly distributed, whereas PV+/Scgn+ interneurons tended to distribute more laterally in the rostral striatum but more medially in caudal striatum (Figure 2C, Supplementary file 1, Figure 2—source data 1). This particular pattern of bias in the distribution of PV+/Scgn+ interneurons is highly unusual in that it has not been described for any other striatal cell population. Along the dorso-ventral axis, PV+/Scgn- interneurons were more likely than PV+/Scgn+ interneurons to display a slight dorsal bias in their localization (Figure 2D, Supplementary file 1, Figure 2—source data 1). Taken together, these data show that the selective expression of Scgn distinguishes two populations of PV+ interneurons that display significantly different spatial distributions in the dorsal striatum of the rat.10.7554/eLife.16088.005Figure 2.PV+/Scgn+ and PV+/Scgn- interneurons have different biases in their distributions in the dorsal striatum of the rat.

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