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Comparative density of CCK- and PV-GABA cells within the cortex and hippocampus.

Whissell PD, Cajanding JD, Fogel N, Kim JC - Front Neuroanat (2015)

Bottom Line: However, the relationship and balance between CCK- and PV-GABA neurons in the inhibitory networks of the brain is currently unclear as the distribution of these cells has never been compared on a large scale.The reverse trend was observed for PV-GABA cells.The intersectional genetic labeling approach employed in the current study expands upon the ability to study molecularly defined subsets of GABAergic neurons.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, University of Toronto, Toronto ON, Canada.

ABSTRACT
Cholecystokinin (CCK)- and parvalbumin (PV)-expressing neurons constitute the two major populations of perisomatic GABAergic neurons in the cortex and the hippocampus. As CCK- and PV-GABA neurons differ in an array of morphological, biochemical and electrophysiological features, it has been proposed that they form distinct inhibitory ensembles which differentially contribute to network oscillations and behavior. However, the relationship and balance between CCK- and PV-GABA neurons in the inhibitory networks of the brain is currently unclear as the distribution of these cells has never been compared on a large scale. Here, we systemically investigated the distribution of CCK- and PV-GABA cells across a wide number of discrete forebrain regions using an intersectional genetic approach. Our analysis revealed several novel trends in the distribution of these cells. While PV-GABA cells were more abundant overall, CCK-GABA cells outnumbered PV-GABA cells in several subregions of the hippocampus, medial prefrontal cortex and ventrolateral temporal cortex. Interestingly, CCK-GABA cells were relatively more abundant in secondary/association areas of the cortex (V2, S2, M2, and AudD/AudV) than they were in corresponding primary areas (V1, S1, M1, and Aud1). The reverse trend was observed for PV-GABA cells. Our findings suggest that the balance between CCK- and PV-GABA cells in a given cortical region is related to the type of processing that area performs; inhibitory networks in the secondary cortex tend to favor the inclusion of CCK-GABA cells more than networks in the primary cortex. The intersectional genetic labeling approach employed in the current study expands upon the ability to study molecularly defined subsets of GABAergic neurons. This technique can be applied to the investigation of neuropathologies which involve disruptions to the GABAergic system, including schizophrenia, stress, maternal immune activation and autism.

No MeSH data available.


Related in: MedlinePlus

Distribution of CCK- and PV-GABA cells within the hippocampus. (A) Hippocampal sections from CCK-Frepe (left) and PV-Frepe mice (right). GFP-labeled cells represent CCK- and PV-GABA cells, respectively. (B) Percentage contribution of CCK-GABA cells (orange) and PV-GABA cells (blue) to the GABA neuron population in each hippocampal subregion. CCK-GABA cells were comparatively more abundant in the dCA1 and vCA1 regions whereas PV-GABA cells were more abundant in the dSub region. (C) The total density of GABA cells, defined as the sum of GFP- and mCherry-labeled cell density, did not differ between CCK- and PV-Frepe mice. (D,E) Distribution of CCK- and PV-GABA cells by hippocampal layer. CCK-GABA cells were most common in the sr layer but were also found in the sp and so layers. PV-GABA cells were more concentrated in the sp layer, but were also found in the so layer. Abbreviations by subregion: dCA1, dorsal CA1, dCA3, dorsal CA3, dDG, dorsal dentate gyrus, dSub, dorsal subiculum, vCA1, ventral CA1, vCA3, ventral CA3 and vDG, ventral dentate gyrus. Abbreviations by layer: hi, hilus, sg, stratum granulosum, sl, stratum lucidum, slm, stratum lacunosum-moleculare, sm, stratum moleculare, so, stratum oriens, sp, stratum pyramidale and sr, stratum radiatum. Significance at the p < 0.05 level is denoted with an asterisk. Scale bar = 500 μM.
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Figure 2: Distribution of CCK- and PV-GABA cells within the hippocampus. (A) Hippocampal sections from CCK-Frepe (left) and PV-Frepe mice (right). GFP-labeled cells represent CCK- and PV-GABA cells, respectively. (B) Percentage contribution of CCK-GABA cells (orange) and PV-GABA cells (blue) to the GABA neuron population in each hippocampal subregion. CCK-GABA cells were comparatively more abundant in the dCA1 and vCA1 regions whereas PV-GABA cells were more abundant in the dSub region. (C) The total density of GABA cells, defined as the sum of GFP- and mCherry-labeled cell density, did not differ between CCK- and PV-Frepe mice. (D,E) Distribution of CCK- and PV-GABA cells by hippocampal layer. CCK-GABA cells were most common in the sr layer but were also found in the sp and so layers. PV-GABA cells were more concentrated in the sp layer, but were also found in the so layer. Abbreviations by subregion: dCA1, dorsal CA1, dCA3, dorsal CA3, dDG, dorsal dentate gyrus, dSub, dorsal subiculum, vCA1, ventral CA1, vCA3, ventral CA3 and vDG, ventral dentate gyrus. Abbreviations by layer: hi, hilus, sg, stratum granulosum, sl, stratum lucidum, slm, stratum lacunosum-moleculare, sm, stratum moleculare, so, stratum oriens, sp, stratum pyramidale and sr, stratum radiatum. Significance at the p < 0.05 level is denoted with an asterisk. Scale bar = 500 μM.

Mentions: In CCK- and PV-Frepe mice, cells labeled with GFP or mCherry were quantified using unbiased automated cell counting. The percentage of CCK- and PV-GABA cells was defined as the percentage of fluorescently labeled cells that were GFP-labeled cells (i.e., GFP cells/[GFP cells + mCherry cells]). In our analysis of the hippocampus, we counted labeled cells in the Cornu Ammonis subfields (CA1, CA3), dentate gyrus (DG) and subiculum (Sub). As the dorsal and ventral hippocampus are often considered anatomically and functionally distinct (Nomura et al., 1997; Strange et al., 2014), dorsal and ventral subregions were defined separately by using the rhinal fissure as a landmark. Subregions above the rhinal fissure were considered to belong to the dorsal hippocampus whereas subregions below were considered to belong to the ventral hippocampus. In total, eight hippocampal subregions were counted (dCA1, dCA3, dDG, dSub, vCA1, vCA3, vDG, and vSub) (Table 1, Figure 2). As our sampling method focused on the intermediate sections of the mouse brain, the caudal vSub was often absent. Accordingly, this region was excluded from analysis.


Comparative density of CCK- and PV-GABA cells within the cortex and hippocampus.

Whissell PD, Cajanding JD, Fogel N, Kim JC - Front Neuroanat (2015)

Distribution of CCK- and PV-GABA cells within the hippocampus. (A) Hippocampal sections from CCK-Frepe (left) and PV-Frepe mice (right). GFP-labeled cells represent CCK- and PV-GABA cells, respectively. (B) Percentage contribution of CCK-GABA cells (orange) and PV-GABA cells (blue) to the GABA neuron population in each hippocampal subregion. CCK-GABA cells were comparatively more abundant in the dCA1 and vCA1 regions whereas PV-GABA cells were more abundant in the dSub region. (C) The total density of GABA cells, defined as the sum of GFP- and mCherry-labeled cell density, did not differ between CCK- and PV-Frepe mice. (D,E) Distribution of CCK- and PV-GABA cells by hippocampal layer. CCK-GABA cells were most common in the sr layer but were also found in the sp and so layers. PV-GABA cells were more concentrated in the sp layer, but were also found in the so layer. Abbreviations by subregion: dCA1, dorsal CA1, dCA3, dorsal CA3, dDG, dorsal dentate gyrus, dSub, dorsal subiculum, vCA1, ventral CA1, vCA3, ventral CA3 and vDG, ventral dentate gyrus. Abbreviations by layer: hi, hilus, sg, stratum granulosum, sl, stratum lucidum, slm, stratum lacunosum-moleculare, sm, stratum moleculare, so, stratum oriens, sp, stratum pyramidale and sr, stratum radiatum. Significance at the p < 0.05 level is denoted with an asterisk. Scale bar = 500 μM.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
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Figure 2: Distribution of CCK- and PV-GABA cells within the hippocampus. (A) Hippocampal sections from CCK-Frepe (left) and PV-Frepe mice (right). GFP-labeled cells represent CCK- and PV-GABA cells, respectively. (B) Percentage contribution of CCK-GABA cells (orange) and PV-GABA cells (blue) to the GABA neuron population in each hippocampal subregion. CCK-GABA cells were comparatively more abundant in the dCA1 and vCA1 regions whereas PV-GABA cells were more abundant in the dSub region. (C) The total density of GABA cells, defined as the sum of GFP- and mCherry-labeled cell density, did not differ between CCK- and PV-Frepe mice. (D,E) Distribution of CCK- and PV-GABA cells by hippocampal layer. CCK-GABA cells were most common in the sr layer but were also found in the sp and so layers. PV-GABA cells were more concentrated in the sp layer, but were also found in the so layer. Abbreviations by subregion: dCA1, dorsal CA1, dCA3, dorsal CA3, dDG, dorsal dentate gyrus, dSub, dorsal subiculum, vCA1, ventral CA1, vCA3, ventral CA3 and vDG, ventral dentate gyrus. Abbreviations by layer: hi, hilus, sg, stratum granulosum, sl, stratum lucidum, slm, stratum lacunosum-moleculare, sm, stratum moleculare, so, stratum oriens, sp, stratum pyramidale and sr, stratum radiatum. Significance at the p < 0.05 level is denoted with an asterisk. Scale bar = 500 μM.
Mentions: In CCK- and PV-Frepe mice, cells labeled with GFP or mCherry were quantified using unbiased automated cell counting. The percentage of CCK- and PV-GABA cells was defined as the percentage of fluorescently labeled cells that were GFP-labeled cells (i.e., GFP cells/[GFP cells + mCherry cells]). In our analysis of the hippocampus, we counted labeled cells in the Cornu Ammonis subfields (CA1, CA3), dentate gyrus (DG) and subiculum (Sub). As the dorsal and ventral hippocampus are often considered anatomically and functionally distinct (Nomura et al., 1997; Strange et al., 2014), dorsal and ventral subregions were defined separately by using the rhinal fissure as a landmark. Subregions above the rhinal fissure were considered to belong to the dorsal hippocampus whereas subregions below were considered to belong to the ventral hippocampus. In total, eight hippocampal subregions were counted (dCA1, dCA3, dDG, dSub, vCA1, vCA3, vDG, and vSub) (Table 1, Figure 2). As our sampling method focused on the intermediate sections of the mouse brain, the caudal vSub was often absent. Accordingly, this region was excluded from analysis.

Bottom Line: However, the relationship and balance between CCK- and PV-GABA neurons in the inhibitory networks of the brain is currently unclear as the distribution of these cells has never been compared on a large scale.The reverse trend was observed for PV-GABA cells.The intersectional genetic labeling approach employed in the current study expands upon the ability to study molecularly defined subsets of GABAergic neurons.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, University of Toronto, Toronto ON, Canada.

ABSTRACT
Cholecystokinin (CCK)- and parvalbumin (PV)-expressing neurons constitute the two major populations of perisomatic GABAergic neurons in the cortex and the hippocampus. As CCK- and PV-GABA neurons differ in an array of morphological, biochemical and electrophysiological features, it has been proposed that they form distinct inhibitory ensembles which differentially contribute to network oscillations and behavior. However, the relationship and balance between CCK- and PV-GABA neurons in the inhibitory networks of the brain is currently unclear as the distribution of these cells has never been compared on a large scale. Here, we systemically investigated the distribution of CCK- and PV-GABA cells across a wide number of discrete forebrain regions using an intersectional genetic approach. Our analysis revealed several novel trends in the distribution of these cells. While PV-GABA cells were more abundant overall, CCK-GABA cells outnumbered PV-GABA cells in several subregions of the hippocampus, medial prefrontal cortex and ventrolateral temporal cortex. Interestingly, CCK-GABA cells were relatively more abundant in secondary/association areas of the cortex (V2, S2, M2, and AudD/AudV) than they were in corresponding primary areas (V1, S1, M1, and Aud1). The reverse trend was observed for PV-GABA cells. Our findings suggest that the balance between CCK- and PV-GABA cells in a given cortical region is related to the type of processing that area performs; inhibitory networks in the secondary cortex tend to favor the inclusion of CCK-GABA cells more than networks in the primary cortex. The intersectional genetic labeling approach employed in the current study expands upon the ability to study molecularly defined subsets of GABAergic neurons. This technique can be applied to the investigation of neuropathologies which involve disruptions to the GABAergic system, including schizophrenia, stress, maternal immune activation and autism.

No MeSH data available.


Related in: MedlinePlus