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

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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

Appositions formed by the axons of PV+ interneurons with the somata of SPNs are associated with the post-synaptic marker gephyrin.(A) Confocal micrograph stack of an SPN cell body, labeled with DARPP-32 (purple), that is apposed by the boutons of a neurobiotin (NB)-labeled axon of a PV+/Scgn+ interneuron (blue). The section has also been labeled with an antibody against the post-synaptic structural protein gephyrin (yellow). Scale bar = 5 µm. (B–F), Single-plane confocal micrographs showing the xy axis and the corresponding orthogonal views; xz (top) and yz (right) of the 5 appositions labeled in A. Axes crossing points are marked by colored lines. The top right corner panel shows a magnification of the apposition in the xy axis. Note that, for each apposition, there is a punctate gephyrin signal located between the axonal bouton and the soma, indicating the presence of a putative GABAergic synapse.DOI:http://dx.doi.org/10.7554/eLife.16088.014
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fig7: Appositions formed by the axons of PV+ interneurons with the somata of SPNs are associated with the post-synaptic marker gephyrin.(A) Confocal micrograph stack of an SPN cell body, labeled with DARPP-32 (purple), that is apposed by the boutons of a neurobiotin (NB)-labeled axon of a PV+/Scgn+ interneuron (blue). The section has also been labeled with an antibody against the post-synaptic structural protein gephyrin (yellow). Scale bar = 5 µm. (B–F), Single-plane confocal micrographs showing the xy axis and the corresponding orthogonal views; xz (top) and yz (right) of the 5 appositions labeled in A. Axes crossing points are marked by colored lines. The top right corner panel shows a magnification of the apposition in the xy axis. Note that, for each apposition, there is a punctate gephyrin signal located between the axonal bouton and the soma, indicating the presence of a putative GABAergic synapse.DOI:http://dx.doi.org/10.7554/eLife.16088.014

Mentions: The axon terminals of dorsal striatal PV+ interneurons/FSIs often form multiple “basket-like” appositions with SPN cell bodies (Koos and Tepper, 1999; Kubota and Kawaguchi, 2000), allowing them to powerfully inhibit SPNs, a mechanism which is thought central to their role in the striatal microcircuit (Tepper and Bolam, 2004). Fully delineating the role of any neuron type requires an understanding of not only its neurochemical/molecular properties and the temporal organization of its activity, but also of the cellular targets that it innervates. With the latter in mind, some of the recorded and neurobiotin-labeled PV+/Scgn+ and PV+/Scgn- interneurons (n = 4 and 4, respectively) were used to gain insight into whether these two cell populations target the same types of SPN to the same extent. We thus compared the prevalence of appositions of the terminal-like axonal varicosities ('boutons') of neurobiotin-labeled PV+/Scgn+ or PV+/Scgn- interneurons with the cell bodies of SPNs (selectively labeled with DARPP-32). In agreement with previous descriptions (Kawaguchi, 1993Sharott et al., 2012), PV+ interneurons exhibited dense local axonal arborizations (see Figure 4) that often formed varicosities in close proximity to (i.e. were apposed to) the somata of SPNs (Figure 7). Whether or not these appositions indicated the presence of functional axo-somatic synapses between PV+ interneurons and SPNs was investigated by simultaneously detecting the presence of gephyrin, which is highly enriched in the post-synaptic membranes of GABAergic synapses (Sigal et al., 2015). Quantification of the overlap between gephyrin puncta and axonal varicosities revealed that appositions between neurobiotin-labeled axonal boutons and SPNs were often the sites of putative GABAergic synapses (Figure 7). Indeed, 69.2 ± 2.4% of appositions (n = 104) made by the axons of PV+/Scgn+ interneurons (n = 3) with SPN somata were associated with discrete puncta of gephyrin immunoreactvity, while 75.5 ± 6.6% of appositions (n = 94) made by the axons of PV+/Scgn- neurons (n = 2) were associated with discrete gephyrin+ puncta. These data suggest that, at the site of an apposition of a PV+ interneuron axonal bouton with a SPN soma, there is a high probability of a GABAergic synapse being formed.10.7554/eLife.16088.014Figure 7.Appositions formed by the axons of PV+ interneurons with the somata of SPNs are associated with the post-synaptic marker gephyrin.


Secretagogin expression delineates functionally-specialized populations of striatal parvalbumin-containing interneurons
Appositions formed by the axons of PV+ interneurons with the somata of SPNs are associated with the post-synaptic marker gephyrin.(A) Confocal micrograph stack of an SPN cell body, labeled with DARPP-32 (purple), that is apposed by the boutons of a neurobiotin (NB)-labeled axon of a PV+/Scgn+ interneuron (blue). The section has also been labeled with an antibody against the post-synaptic structural protein gephyrin (yellow). Scale bar = 5 µm. (B–F), Single-plane confocal micrographs showing the xy axis and the corresponding orthogonal views; xz (top) and yz (right) of the 5 appositions labeled in A. Axes crossing points are marked by colored lines. The top right corner panel shows a magnification of the apposition in the xy axis. Note that, for each apposition, there is a punctate gephyrin signal located between the axonal bouton and the soma, indicating the presence of a putative GABAergic synapse.DOI:http://dx.doi.org/10.7554/eLife.16088.014
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fig7: Appositions formed by the axons of PV+ interneurons with the somata of SPNs are associated with the post-synaptic marker gephyrin.(A) Confocal micrograph stack of an SPN cell body, labeled with DARPP-32 (purple), that is apposed by the boutons of a neurobiotin (NB)-labeled axon of a PV+/Scgn+ interneuron (blue). The section has also been labeled with an antibody against the post-synaptic structural protein gephyrin (yellow). Scale bar = 5 µm. (B–F), Single-plane confocal micrographs showing the xy axis and the corresponding orthogonal views; xz (top) and yz (right) of the 5 appositions labeled in A. Axes crossing points are marked by colored lines. The top right corner panel shows a magnification of the apposition in the xy axis. Note that, for each apposition, there is a punctate gephyrin signal located between the axonal bouton and the soma, indicating the presence of a putative GABAergic synapse.DOI:http://dx.doi.org/10.7554/eLife.16088.014
Mentions: The axon terminals of dorsal striatal PV+ interneurons/FSIs often form multiple “basket-like” appositions with SPN cell bodies (Koos and Tepper, 1999; Kubota and Kawaguchi, 2000), allowing them to powerfully inhibit SPNs, a mechanism which is thought central to their role in the striatal microcircuit (Tepper and Bolam, 2004). Fully delineating the role of any neuron type requires an understanding of not only its neurochemical/molecular properties and the temporal organization of its activity, but also of the cellular targets that it innervates. With the latter in mind, some of the recorded and neurobiotin-labeled PV+/Scgn+ and PV+/Scgn- interneurons (n = 4 and 4, respectively) were used to gain insight into whether these two cell populations target the same types of SPN to the same extent. We thus compared the prevalence of appositions of the terminal-like axonal varicosities ('boutons') of neurobiotin-labeled PV+/Scgn+ or PV+/Scgn- interneurons with the cell bodies of SPNs (selectively labeled with DARPP-32). In agreement with previous descriptions (Kawaguchi, 1993Sharott et al., 2012), PV+ interneurons exhibited dense local axonal arborizations (see Figure 4) that often formed varicosities in close proximity to (i.e. were apposed to) the somata of SPNs (Figure 7). Whether or not these appositions indicated the presence of functional axo-somatic synapses between PV+ interneurons and SPNs was investigated by simultaneously detecting the presence of gephyrin, which is highly enriched in the post-synaptic membranes of GABAergic synapses (Sigal et al., 2015). Quantification of the overlap between gephyrin puncta and axonal varicosities revealed that appositions between neurobiotin-labeled axonal boutons and SPNs were often the sites of putative GABAergic synapses (Figure 7). Indeed, 69.2 ± 2.4% of appositions (n = 104) made by the axons of PV+/Scgn+ interneurons (n = 3) with SPN somata were associated with discrete puncta of gephyrin immunoreactvity, while 75.5 ± 6.6% of appositions (n = 94) made by the axons of PV+/Scgn- neurons (n = 2) were associated with discrete gephyrin+ puncta. These data suggest that, at the site of an apposition of a PV+ interneuron axonal bouton with a SPN soma, there is a high probability of a GABAergic synapse being formed.10.7554/eLife.16088.014Figure 7.Appositions formed by the axons of PV+ interneurons with the somata of SPNs are associated with the post-synaptic marker gephyrin.

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