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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.


PV+/Scgn- and PV+/Scgn+ striatal interneurons selectively target the somata of SPNs in the direct or indirect pathway.(Ai) Confocal fluorescent micrograph stack of a neurobiotin (NB)-labeled axon of a PV+/Scgn- interneuron (green) targeting a SPN revealed with DARRP-32 (purple). The interneuron axon forms 4 appositions (numbered white arrows) with the SPN soma. (Aii) The SPN expresses preproenkephalin (PPE, white), indicating it is in the indirect pathway (iSPN). (Aiii, Aiv) Single-plane confocal micrographs verifying that each of the 4 boutons is closely apposed to the SPN soma. (Bi) Confocal fluorescent micrograph stack of the NB-labeled axon of a PV+/Scgn+ interneuron (blue) traversing close to two SPNs. The axon forms 3 appositions (white arrows) with the SPN soma on the left, and appears to form a single apposition (red arrow) with the SPN on right. (Bii) The right SPN expresses PPE (iSPN), while the left SPN does not, indicating it is in the direct pathway (dSPN). (Biii, Biv), Single-plane confocal micrographs verifying that boutons 1–3 are apposed to the soma of the dSPN, while bouton 4 is not directly apposed to the iSPN. (C) Quantitative analyses of the NB-labeled axonal boutons of PV+/Scgn- and PV+/Scgn+ interneurons revealed that the axons of PV+/Scgn- interneurons were more likely to be opposed to the somata of SPNs. (D) Histogram of the frequency of different numbers of appositions formed with an individual SPN soma for both types of interneuron. (E) The axons of PV+/Scgn- interneurons were more likely than the axons of PV+/Scgn+ interneurons to target the somata of PPE+ SPNs of the indirect pathway.(A,B, scale bars are 20 µm.)DOI:http://dx.doi.org/10.7554/eLife.16088.01510.7554/eLife.16088.016Figure 8—source data 1.Source data for Figure 8C,D,E.DOI:http://dx.doi.org/10.7554/eLife.16088.016
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fig8: PV+/Scgn- and PV+/Scgn+ striatal interneurons selectively target the somata of SPNs in the direct or indirect pathway.(Ai) Confocal fluorescent micrograph stack of a neurobiotin (NB)-labeled axon of a PV+/Scgn- interneuron (green) targeting a SPN revealed with DARRP-32 (purple). The interneuron axon forms 4 appositions (numbered white arrows) with the SPN soma. (Aii) The SPN expresses preproenkephalin (PPE, white), indicating it is in the indirect pathway (iSPN). (Aiii, Aiv) Single-plane confocal micrographs verifying that each of the 4 boutons is closely apposed to the SPN soma. (Bi) Confocal fluorescent micrograph stack of the NB-labeled axon of a PV+/Scgn+ interneuron (blue) traversing close to two SPNs. The axon forms 3 appositions (white arrows) with the SPN soma on the left, and appears to form a single apposition (red arrow) with the SPN on right. (Bii) The right SPN expresses PPE (iSPN), while the left SPN does not, indicating it is in the direct pathway (dSPN). (Biii, Biv), Single-plane confocal micrographs verifying that boutons 1–3 are apposed to the soma of the dSPN, while bouton 4 is not directly apposed to the iSPN. (C) Quantitative analyses of the NB-labeled axonal boutons of PV+/Scgn- and PV+/Scgn+ interneurons revealed that the axons of PV+/Scgn- interneurons were more likely to be opposed to the somata of SPNs. (D) Histogram of the frequency of different numbers of appositions formed with an individual SPN soma for both types of interneuron. (E) The axons of PV+/Scgn- interneurons were more likely than the axons of PV+/Scgn+ interneurons to target the somata of PPE+ SPNs of the indirect pathway.(A,B, scale bars are 20 µm.)DOI:http://dx.doi.org/10.7554/eLife.16088.01510.7554/eLife.16088.016Figure 8—source data 1.Source data for Figure 8C,D,E.DOI:http://dx.doi.org/10.7554/eLife.16088.016

Mentions: Previous work has shown that the proportion of somatic (as compared to dendritic) synapses formed by the axons of individual PV+ interneurons ranges from 7 to 58% (Kubota and Kawaguchi, 2000). Next we examined whether any of this variability could be explained by systematic differences in innervation of SPN somata by the two populations of PV+ interneuron. Neurobiotin-labeled boutons of PV+/Scgn- interneurons (neurons = 4, boutons = 347) were almost twice as likely as those of PV+/Scgn+ interneurons (neurons = 3, boutons = 709) to appose the somata of SPNs (Figure 8C; Fisher Exact Test, p<0.001. Figure 8—source data 1). A complementary analysis showed that SPN somata that were apposed to at least one axonal bouton of a PV+ interneuron received a significantly greater number of appositions from the axons of PV+/Scgn- interneurons (n = 46 SPN somata) as compared to appositions from the axons of PV+/Scgn+ interneurons (n = 44 SPN somata; Figure 8D, Mann Whitney, p=0.009. Figure 8—source data 1). Taken together, these data not only show that the axons of both PV+/Scgn- interneurons and PV+/Scgn+ interneurons innervate SPN cell bodies, but also that the former interneuron population is more likely to do so and with more appositions per targeted SPN.10.7554/eLife.16088.015Figure 8.PV+/Scgn- and PV+/Scgn+ striatal interneurons selectively target the somata of SPNs in the direct or indirect pathway.


Secretagogin expression delineates functionally-specialized populations of striatal parvalbumin-containing interneurons
PV+/Scgn- and PV+/Scgn+ striatal interneurons selectively target the somata of SPNs in the direct or indirect pathway.(Ai) Confocal fluorescent micrograph stack of a neurobiotin (NB)-labeled axon of a PV+/Scgn- interneuron (green) targeting a SPN revealed with DARRP-32 (purple). The interneuron axon forms 4 appositions (numbered white arrows) with the SPN soma. (Aii) The SPN expresses preproenkephalin (PPE, white), indicating it is in the indirect pathway (iSPN). (Aiii, Aiv) Single-plane confocal micrographs verifying that each of the 4 boutons is closely apposed to the SPN soma. (Bi) Confocal fluorescent micrograph stack of the NB-labeled axon of a PV+/Scgn+ interneuron (blue) traversing close to two SPNs. The axon forms 3 appositions (white arrows) with the SPN soma on the left, and appears to form a single apposition (red arrow) with the SPN on right. (Bii) The right SPN expresses PPE (iSPN), while the left SPN does not, indicating it is in the direct pathway (dSPN). (Biii, Biv), Single-plane confocal micrographs verifying that boutons 1–3 are apposed to the soma of the dSPN, while bouton 4 is not directly apposed to the iSPN. (C) Quantitative analyses of the NB-labeled axonal boutons of PV+/Scgn- and PV+/Scgn+ interneurons revealed that the axons of PV+/Scgn- interneurons were more likely to be opposed to the somata of SPNs. (D) Histogram of the frequency of different numbers of appositions formed with an individual SPN soma for both types of interneuron. (E) The axons of PV+/Scgn- interneurons were more likely than the axons of PV+/Scgn+ interneurons to target the somata of PPE+ SPNs of the indirect pathway.(A,B, scale bars are 20 µm.)DOI:http://dx.doi.org/10.7554/eLife.16088.01510.7554/eLife.16088.016Figure 8—source data 1.Source data for Figure 8C,D,E.DOI:http://dx.doi.org/10.7554/eLife.16088.016
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fig8: PV+/Scgn- and PV+/Scgn+ striatal interneurons selectively target the somata of SPNs in the direct or indirect pathway.(Ai) Confocal fluorescent micrograph stack of a neurobiotin (NB)-labeled axon of a PV+/Scgn- interneuron (green) targeting a SPN revealed with DARRP-32 (purple). The interneuron axon forms 4 appositions (numbered white arrows) with the SPN soma. (Aii) The SPN expresses preproenkephalin (PPE, white), indicating it is in the indirect pathway (iSPN). (Aiii, Aiv) Single-plane confocal micrographs verifying that each of the 4 boutons is closely apposed to the SPN soma. (Bi) Confocal fluorescent micrograph stack of the NB-labeled axon of a PV+/Scgn+ interneuron (blue) traversing close to two SPNs. The axon forms 3 appositions (white arrows) with the SPN soma on the left, and appears to form a single apposition (red arrow) with the SPN on right. (Bii) The right SPN expresses PPE (iSPN), while the left SPN does not, indicating it is in the direct pathway (dSPN). (Biii, Biv), Single-plane confocal micrographs verifying that boutons 1–3 are apposed to the soma of the dSPN, while bouton 4 is not directly apposed to the iSPN. (C) Quantitative analyses of the NB-labeled axonal boutons of PV+/Scgn- and PV+/Scgn+ interneurons revealed that the axons of PV+/Scgn- interneurons were more likely to be opposed to the somata of SPNs. (D) Histogram of the frequency of different numbers of appositions formed with an individual SPN soma for both types of interneuron. (E) The axons of PV+/Scgn- interneurons were more likely than the axons of PV+/Scgn+ interneurons to target the somata of PPE+ SPNs of the indirect pathway.(A,B, scale bars are 20 µm.)DOI:http://dx.doi.org/10.7554/eLife.16088.01510.7554/eLife.16088.016Figure 8—source data 1.Source data for Figure 8C,D,E.DOI:http://dx.doi.org/10.7554/eLife.16088.016
Mentions: Previous work has shown that the proportion of somatic (as compared to dendritic) synapses formed by the axons of individual PV+ interneurons ranges from 7 to 58% (Kubota and Kawaguchi, 2000). Next we examined whether any of this variability could be explained by systematic differences in innervation of SPN somata by the two populations of PV+ interneuron. Neurobiotin-labeled boutons of PV+/Scgn- interneurons (neurons = 4, boutons = 347) were almost twice as likely as those of PV+/Scgn+ interneurons (neurons = 3, boutons = 709) to appose the somata of SPNs (Figure 8C; Fisher Exact Test, p<0.001. Figure 8—source data 1). A complementary analysis showed that SPN somata that were apposed to at least one axonal bouton of a PV+ interneuron received a significantly greater number of appositions from the axons of PV+/Scgn- interneurons (n = 46 SPN somata) as compared to appositions from the axons of PV+/Scgn+ interneurons (n = 44 SPN somata; Figure 8D, Mann Whitney, p=0.009. Figure 8—source data 1). Taken together, these data not only show that the axons of both PV+/Scgn- interneurons and PV+/Scgn+ interneurons innervate SPN cell bodies, but also that the former interneuron population is more likely to do so and with more appositions per targeted SPN.10.7554/eLife.16088.015Figure 8.PV+/Scgn- and PV+/Scgn+ striatal interneurons selectively target the somata of SPNs in the direct or indirect pathway.

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.