TY - JOUR
T1 - Ensemble-specific deficit in neuronal intrinsic excitability in aged mice
AU - Chen, Lingxuan
AU - Francisco, Taylor R.
AU - Baggetta, Austin M.
AU - Zaki, Yosif
AU - Ramirez, Steve
AU - Clem, Roger L.
AU - Shuman, Tristan
AU - Cai, Denise J.
N1 - Funding Information:
This work was supported by the Brain Research Foundation Award , Klingenstein-Simons Fellowship , NARSAD Young Investigator Award , McKnight Memory and Cognitive Disorder Award , One Mind-Otsuka Rising Star Research Award , Mount Sinai Distinguished Scholar Award , DP2 MH122399-01 , and R01 MH120162-01A1 to DJC; the CURE Taking Flight Award , American Epilepsy Society Junior Investigator Award , R03 NS111493 , R21 DA049568 , R01 NS116357 , and RF1 AG072497 to TS; R01 124880 and R01 116445 to RLC; and an NIH Early Independence Award DP5 OD023106-01 , NIH Transformative R01 Award , a Ludwig Family Foundation grant , and McKnight Foundation Memory and Cognitive Disorders Award to SR . We thank Stellate Communications for assistance with the preparation of this manuscript.
Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2023/3
Y1 - 2023/3
N2 - With the prevalence of age-related cognitive deficits on the rise, it is essential to identify cellular and circuit alterations that contribute to age-related memory impairment. Increased intrinsic neuronal excitability after learning is important for memory consolidation, and changes to this process could underlie memory impairment in old age. Some studies find age-related deficits in hippocampal neuronal excitability that correlate with memory impairment but others do not, possibly due to selective changes only in activated neural ensembles. Thus, we tagged CA1 neurons activated during learning and recorded their intrinsic excitability 5 hours or 7 days post-training. Adult mice exhibited increased neuronal excitability 5 hours after learning, specifically in ensemble (learning-activated) CA1 neurons. As expected, ensemble excitability returned to baseline 7 days post-training. In aged mice, there was no ensemble-specific excitability increase after learning, which was associated with impaired hippocampal memory performance. These results suggest that CA1 may be susceptible to age-related impairments in post-learning ensemble excitability and underscore the need to selectively measure ensemble-specific changes in the brain.
AB - With the prevalence of age-related cognitive deficits on the rise, it is essential to identify cellular and circuit alterations that contribute to age-related memory impairment. Increased intrinsic neuronal excitability after learning is important for memory consolidation, and changes to this process could underlie memory impairment in old age. Some studies find age-related deficits in hippocampal neuronal excitability that correlate with memory impairment but others do not, possibly due to selective changes only in activated neural ensembles. Thus, we tagged CA1 neurons activated during learning and recorded their intrinsic excitability 5 hours or 7 days post-training. Adult mice exhibited increased neuronal excitability 5 hours after learning, specifically in ensemble (learning-activated) CA1 neurons. As expected, ensemble excitability returned to baseline 7 days post-training. In aged mice, there was no ensemble-specific excitability increase after learning, which was associated with impaired hippocampal memory performance. These results suggest that CA1 may be susceptible to age-related impairments in post-learning ensemble excitability and underscore the need to selectively measure ensemble-specific changes in the brain.
KW - Aging
KW - Ensemble tagging
KW - Learning
KW - Neuronal intrinsic excitability
KW - Novel object location
KW - Whole-cell patch clamp
UR - http://www.scopus.com/inward/record.url?scp=85146448804&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2022.12.007
DO - 10.1016/j.neurobiolaging.2022.12.007
M3 - Article
AN - SCOPUS:85146448804
SN - 0197-4580
VL - 123
SP - 92
EP - 97
JO - Neurobiology of Aging
JF - Neurobiology of Aging
ER -