Limits...
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.


A large subpopulation of PV+ interneurons co-express Scgn in the dorsal striatum of rats, but not in mice.(A–F), Co-expression of PV and Scgn in the dorsal striatum of the mouse. (A, B) Immunofluorescence signals for Scgn (arrows), the pan-neuronal marker NeuN (A) and SPN-specific marker, Ctip2 (B). Scgn+ cells express NeuN, but not Ctip2, indicating they are interneurons. (C, D), Immunofluorescence signals for PV and Scgn. The vast majority of Scgn+ neurons did not co-express PV (C, white arrow) although a few did (D). (E, F) Densities and numbers of interneurons expressing combinations of PV and/or Scgn. PV and Scgn were seldom expressed by the same interneurons in the mouse dorsal striatum. (G–L) As in A–F, but all data are from the dorsal striatum of rat. (G, H) Scgn+ cells express NeuN, but not Ctip2, indicating they are interneurons. (I, J) In contrast to mouse, Scgn+ interneurons that co-expressed PV were common (I, white arrow), as were those that did not (J, white arrow,). (K, L) Densities and numbers of interneurons expressing combinations of PV and/or Scgn in the rat. About one half of Scgn+ interneurons co-expressed PV (K). About one quarter of PV+ interneurons co-expressed Scgn (L). (Scale bars A–D and G–J, 20 µm)DOI:http://dx.doi.org/10.7554/eLife.16088.00210.7554/eLife.16088.003Figure 1—source data 1.Source data for Figures 1E,F,K,L.DOI:http://dx.doi.org/10.7554/eLife.16088.003
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5036963&req=5

fig1: A large subpopulation of PV+ interneurons co-express Scgn in the dorsal striatum of rats, but not in mice.(A–F), Co-expression of PV and Scgn in the dorsal striatum of the mouse. (A, B) Immunofluorescence signals for Scgn (arrows), the pan-neuronal marker NeuN (A) and SPN-specific marker, Ctip2 (B). Scgn+ cells express NeuN, but not Ctip2, indicating they are interneurons. (C, D), Immunofluorescence signals for PV and Scgn. The vast majority of Scgn+ neurons did not co-express PV (C, white arrow) although a few did (D). (E, F) Densities and numbers of interneurons expressing combinations of PV and/or Scgn. PV and Scgn were seldom expressed by the same interneurons in the mouse dorsal striatum. (G–L) As in A–F, but all data are from the dorsal striatum of rat. (G, H) Scgn+ cells express NeuN, but not Ctip2, indicating they are interneurons. (I, J) In contrast to mouse, Scgn+ interneurons that co-expressed PV were common (I, white arrow), as were those that did not (J, white arrow,). (K, L) Densities and numbers of interneurons expressing combinations of PV and/or Scgn in the rat. About one half of Scgn+ interneurons co-expressed PV (K). About one quarter of PV+ interneurons co-expressed Scgn (L). (Scale bars A–D and G–J, 20 µm)DOI:http://dx.doi.org/10.7554/eLife.16088.00210.7554/eLife.16088.003Figure 1—source data 1.Source data for Figures 1E,F,K,L.DOI:http://dx.doi.org/10.7554/eLife.16088.003

Mentions: In the adult mouse, the calcium-binding protein secretagogin (Scgn) is expressed by some GABAergic, but not cholinergic, striatal neurons (Mulder et al., 2009). To test whether these neurons also express PV, we examined the expression of Scgn and PV across the mouse dorsal striatum using unbiased stereological methods. All striatal Scgn+ cells co-expressed the ‘pan-neuronal’ marker NeuN, but not the SPN-specific marker Ctip2 (Arlotta et al., 2008) (Figure 1A,B), indicating that Scgn is exclusively expressed by interneurons. However, interneurons that co-expressed PV and Scgn were rare. Indeed, the vast majority of Scgn+ interneurons did not co-express PV and vice versa (Figure 1C–F, Figure 1—source data 1). Thus, the previously identified population of GABAergic Scgn+ neurons in mice (Mulder et al., 2009) are interneurons, but not PV-expressing interneurons.10.7554/eLife.16088.002Figure 1.A large subpopulation of PV+ interneurons co-express Scgn in the dorsal striatum of rats, but not in mice.


Secretagogin expression delineates functionally-specialized populations of striatal parvalbumin-containing interneurons
A large subpopulation of PV+ interneurons co-express Scgn in the dorsal striatum of rats, but not in mice.(A–F), Co-expression of PV and Scgn in the dorsal striatum of the mouse. (A, B) Immunofluorescence signals for Scgn (arrows), the pan-neuronal marker NeuN (A) and SPN-specific marker, Ctip2 (B). Scgn+ cells express NeuN, but not Ctip2, indicating they are interneurons. (C, D), Immunofluorescence signals for PV and Scgn. The vast majority of Scgn+ neurons did not co-express PV (C, white arrow) although a few did (D). (E, F) Densities and numbers of interneurons expressing combinations of PV and/or Scgn. PV and Scgn were seldom expressed by the same interneurons in the mouse dorsal striatum. (G–L) As in A–F, but all data are from the dorsal striatum of rat. (G, H) Scgn+ cells express NeuN, but not Ctip2, indicating they are interneurons. (I, J) In contrast to mouse, Scgn+ interneurons that co-expressed PV were common (I, white arrow), as were those that did not (J, white arrow,). (K, L) Densities and numbers of interneurons expressing combinations of PV and/or Scgn in the rat. About one half of Scgn+ interneurons co-expressed PV (K). About one quarter of PV+ interneurons co-expressed Scgn (L). (Scale bars A–D and G–J, 20 µm)DOI:http://dx.doi.org/10.7554/eLife.16088.00210.7554/eLife.16088.003Figure 1—source data 1.Source data for Figures 1E,F,K,L.DOI:http://dx.doi.org/10.7554/eLife.16088.003
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5036963&req=5

fig1: A large subpopulation of PV+ interneurons co-express Scgn in the dorsal striatum of rats, but not in mice.(A–F), Co-expression of PV and Scgn in the dorsal striatum of the mouse. (A, B) Immunofluorescence signals for Scgn (arrows), the pan-neuronal marker NeuN (A) and SPN-specific marker, Ctip2 (B). Scgn+ cells express NeuN, but not Ctip2, indicating they are interneurons. (C, D), Immunofluorescence signals for PV and Scgn. The vast majority of Scgn+ neurons did not co-express PV (C, white arrow) although a few did (D). (E, F) Densities and numbers of interneurons expressing combinations of PV and/or Scgn. PV and Scgn were seldom expressed by the same interneurons in the mouse dorsal striatum. (G–L) As in A–F, but all data are from the dorsal striatum of rat. (G, H) Scgn+ cells express NeuN, but not Ctip2, indicating they are interneurons. (I, J) In contrast to mouse, Scgn+ interneurons that co-expressed PV were common (I, white arrow), as were those that did not (J, white arrow,). (K, L) Densities and numbers of interneurons expressing combinations of PV and/or Scgn in the rat. About one half of Scgn+ interneurons co-expressed PV (K). About one quarter of PV+ interneurons co-expressed Scgn (L). (Scale bars A–D and G–J, 20 µm)DOI:http://dx.doi.org/10.7554/eLife.16088.00210.7554/eLife.16088.003Figure 1—source data 1.Source data for Figures 1E,F,K,L.DOI:http://dx.doi.org/10.7554/eLife.16088.003
Mentions: In the adult mouse, the calcium-binding protein secretagogin (Scgn) is expressed by some GABAergic, but not cholinergic, striatal neurons (Mulder et al., 2009). To test whether these neurons also express PV, we examined the expression of Scgn and PV across the mouse dorsal striatum using unbiased stereological methods. All striatal Scgn+ cells co-expressed the ‘pan-neuronal’ marker NeuN, but not the SPN-specific marker Ctip2 (Arlotta et al., 2008) (Figure 1A,B), indicating that Scgn is exclusively expressed by interneurons. However, interneurons that co-expressed PV and Scgn were rare. Indeed, the vast majority of Scgn+ interneurons did not co-express PV and vice versa (Figure 1C–F, Figure 1—source data 1). Thus, the previously identified population of GABAergic Scgn+ neurons in mice (Mulder et al., 2009) are interneurons, but not PV-expressing interneurons.10.7554/eLife.16088.002Figure 1.A large subpopulation of PV+ interneurons co-express Scgn in the dorsal striatum of rats, but not in mice.

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.