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Region-Specific Disruption of Adenylate Cyclase Type 1 Gene Differentially Affects Somatosensorimotor Behaviors in Mice(1,2,3).

Arakawa H, Akkentli F, Erzurumlu RS - eNeuro (2014)

Bottom Line: Neural modules in the primary somatosensory (SI) cortex, the barrels, which represent the topographic distribution of the whiskers on the snout, failed to form (Welker et al., 1996; Abdel-Majid et al., 1998).To what extent does patterning of the cortical somatosensory body map play a role in sensorimotor behaviors?Contrary to intuitive expectations that any region-specific or global disruption of the AC1 function would lead to similar behavioral phenotypes, we found significant differences in the degree of impairment between these strains.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Anatomy and Neurobiology, University of Maryland School of Medicine , Baltimore, Maryland 21201.

ABSTRACT
Cover FigureRegion-specific adenylyl cyclase 1 (AC1) loss of function differentially affects both patterning and sensorimotor behaviors in mice. AC1 is expressed at all levels of the somatosensory pathway and plays a major role in refinement and patterning of topographic sensory maps. Cortex-specific AC1 loss of function (CxAC1KO mice) does not affect barrel patterning and activation of specific barrels corresponding to stimulated whiskers and does not impair sensorimotor behaviors. While global (AC1KO) and thalamus-specific (ThAC1KO) AC1 loss of function leads to absence of barrel patterns, selective whisker stimulation activates topographically aligned cortical loci. Despite functional topography of the whisker-barrel cortex, sensorimotor and social behaviors are impaired, indicating the importance of patterning of topographical sensory maps in the neocortex. Adenylate cyclase type I (AC1) is primarily, and, abundantly, expressed in the brain. Intracellular calcium/calmodulin increases regulate AC1 in an activity-dependent manner. Upon stimulation, AC1 produces cAMP and it is involved in the patterning and the refinement of neural circuits. In mice, spontaneous mutations or targeted deletion of the Adcy1 gene, which encodes AC1, resulted in neuronal pattern formation defects. Neural modules in the primary somatosensory (SI) cortex, the barrels, which represent the topographic distribution of the whiskers on the snout, failed to form (Welker et al., 1996; Abdel-Majid et al., 1998). Cortex- or thalamus-specific Adcy1 deletions led to different cortical pattern phenotypes, with thalamus-specific disruption phenotype being more severe (Iwasato et al., 2008; Suzuki et al., 2013). Despite the absence of barrels in the "barrelless"/Adcy1 mice, thalamocortical terminal bouton density and activation of cortical zones following whisker stimulation were roughly topographic (Abdel-Majid et al., 1998; Gheorghita et al., 2006). To what extent does patterning of the cortical somatosensory body map play a role in sensorimotor behaviors? In this study, we tested mice with global, cortical, or thalamic loss of AC1 function in a battery of sensorimotor and social behavior tests and compared them to mice with all of the whiskers clipped. Contrary to intuitive expectations that any region-specific or global disruption of the AC1 function would lead to similar behavioral phenotypes, we found significant differences in the degree of impairment between these strains.

No MeSH data available.


Related in: MedlinePlus

Social behavior. A, B, In the social behavior test, there was no difference in the duration of social contacts, F(2,23) = 0.084, p = 0.9201. However, AC1KO mice displayed a notable increment of flight response to the intruder’s contacts from the front, F(2,23) = 7.662, p = 0.0028, and back sides, F(2,23) = 48.434, p = 0.0001, compared with WT or WC mice. C, D, In comparisons of the second group of mice, there was no difference in the duration of social contacts, F(2,21) = 5.896, p = 0.093. However, ThAC1KO mice displayed a greater flight response to the intruder’s contacts from the front, F(2,21) = 25.792, p = 0.0001, and back sides, F(2,21) = 46.706, p < 0.0001, compared with either CxAC1KO or AC1ff mice. All data are expressed as mean ± SEM * indicates significant differences between strains, # indicates significant differences between trials.
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Figure 5: Social behavior. A, B, In the social behavior test, there was no difference in the duration of social contacts, F(2,23) = 0.084, p = 0.9201. However, AC1KO mice displayed a notable increment of flight response to the intruder’s contacts from the front, F(2,23) = 7.662, p = 0.0028, and back sides, F(2,23) = 48.434, p = 0.0001, compared with WT or WC mice. C, D, In comparisons of the second group of mice, there was no difference in the duration of social contacts, F(2,21) = 5.896, p = 0.093. However, ThAC1KO mice displayed a greater flight response to the intruder’s contacts from the front, F(2,21) = 25.792, p = 0.0001, and back sides, F(2,21) = 46.706, p < 0.0001, compared with either CxAC1KO or AC1ff mice. All data are expressed as mean ± SEM * indicates significant differences between strains, # indicates significant differences between trials.

Mentions: Experimental design: random-design


Region-Specific Disruption of Adenylate Cyclase Type 1 Gene Differentially Affects Somatosensorimotor Behaviors in Mice(1,2,3).

Arakawa H, Akkentli F, Erzurumlu RS - eNeuro (2014)

Social behavior. A, B, In the social behavior test, there was no difference in the duration of social contacts, F(2,23) = 0.084, p = 0.9201. However, AC1KO mice displayed a notable increment of flight response to the intruder’s contacts from the front, F(2,23) = 7.662, p = 0.0028, and back sides, F(2,23) = 48.434, p = 0.0001, compared with WT or WC mice. C, D, In comparisons of the second group of mice, there was no difference in the duration of social contacts, F(2,21) = 5.896, p = 0.093. However, ThAC1KO mice displayed a greater flight response to the intruder’s contacts from the front, F(2,21) = 25.792, p = 0.0001, and back sides, F(2,21) = 46.706, p < 0.0001, compared with either CxAC1KO or AC1ff mice. All data are expressed as mean ± SEM * indicates significant differences between strains, # indicates significant differences between trials.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4596139&req=5

Figure 5: Social behavior. A, B, In the social behavior test, there was no difference in the duration of social contacts, F(2,23) = 0.084, p = 0.9201. However, AC1KO mice displayed a notable increment of flight response to the intruder’s contacts from the front, F(2,23) = 7.662, p = 0.0028, and back sides, F(2,23) = 48.434, p = 0.0001, compared with WT or WC mice. C, D, In comparisons of the second group of mice, there was no difference in the duration of social contacts, F(2,21) = 5.896, p = 0.093. However, ThAC1KO mice displayed a greater flight response to the intruder’s contacts from the front, F(2,21) = 25.792, p = 0.0001, and back sides, F(2,21) = 46.706, p < 0.0001, compared with either CxAC1KO or AC1ff mice. All data are expressed as mean ± SEM * indicates significant differences between strains, # indicates significant differences between trials.
Mentions: Experimental design: random-design

Bottom Line: Neural modules in the primary somatosensory (SI) cortex, the barrels, which represent the topographic distribution of the whiskers on the snout, failed to form (Welker et al., 1996; Abdel-Majid et al., 1998).To what extent does patterning of the cortical somatosensory body map play a role in sensorimotor behaviors?Contrary to intuitive expectations that any region-specific or global disruption of the AC1 function would lead to similar behavioral phenotypes, we found significant differences in the degree of impairment between these strains.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Anatomy and Neurobiology, University of Maryland School of Medicine , Baltimore, Maryland 21201.

ABSTRACT
Cover FigureRegion-specific adenylyl cyclase 1 (AC1) loss of function differentially affects both patterning and sensorimotor behaviors in mice. AC1 is expressed at all levels of the somatosensory pathway and plays a major role in refinement and patterning of topographic sensory maps. Cortex-specific AC1 loss of function (CxAC1KO mice) does not affect barrel patterning and activation of specific barrels corresponding to stimulated whiskers and does not impair sensorimotor behaviors. While global (AC1KO) and thalamus-specific (ThAC1KO) AC1 loss of function leads to absence of barrel patterns, selective whisker stimulation activates topographically aligned cortical loci. Despite functional topography of the whisker-barrel cortex, sensorimotor and social behaviors are impaired, indicating the importance of patterning of topographical sensory maps in the neocortex. Adenylate cyclase type I (AC1) is primarily, and, abundantly, expressed in the brain. Intracellular calcium/calmodulin increases regulate AC1 in an activity-dependent manner. Upon stimulation, AC1 produces cAMP and it is involved in the patterning and the refinement of neural circuits. In mice, spontaneous mutations or targeted deletion of the Adcy1 gene, which encodes AC1, resulted in neuronal pattern formation defects. Neural modules in the primary somatosensory (SI) cortex, the barrels, which represent the topographic distribution of the whiskers on the snout, failed to form (Welker et al., 1996; Abdel-Majid et al., 1998). Cortex- or thalamus-specific Adcy1 deletions led to different cortical pattern phenotypes, with thalamus-specific disruption phenotype being more severe (Iwasato et al., 2008; Suzuki et al., 2013). Despite the absence of barrels in the "barrelless"/Adcy1 mice, thalamocortical terminal bouton density and activation of cortical zones following whisker stimulation were roughly topographic (Abdel-Majid et al., 1998; Gheorghita et al., 2006). To what extent does patterning of the cortical somatosensory body map play a role in sensorimotor behaviors? In this study, we tested mice with global, cortical, or thalamic loss of AC1 function in a battery of sensorimotor and social behavior tests and compared them to mice with all of the whiskers clipped. Contrary to intuitive expectations that any region-specific or global disruption of the AC1 function would lead to similar behavioral phenotypes, we found significant differences in the degree of impairment between these strains.

No MeSH data available.


Related in: MedlinePlus