Combined administration of levetiracetam and valproic acid attenuates age-related hyperactivity of CA3 place cells, reduces place field area, and increases spatial information content in aged rat hippocampus.

Authors:
Dr. Marcia Ratner, PhD, DABT
Dr. Marcia Ratner, PhD, DABT
Department of Pharmacology and Experimental Therapeutics,Boston University School of Medicine
Project Manager
Toxicology, Neurology, Pharmacology
Boston, Massachusetts | United States

Hippocampus 2015 Dec 14;25(12):1541-55. Epub 2015 Jul 14.

Laboratory of Molecular Neurobiology, Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts.

Learning and memory deficits associated with age-related mild cognitive impairment have long been attributed to impaired processing within the hippocampus. Hyperactivity within the hippocampal CA3 region that is associated with aging is mediated in part by a loss of functional inhibitory interneurons and thought to underlie impaired performance in spatial memory tasks, including the abnormal tendency in aged animals to pattern complete spatial representations. Here, we asked whether the spatial firing patterns of simultaneously recorded CA3 and CA1 neurons in young and aged rats could be manipulated pharmacologically to selectively reduce CA3 hyperactivity and thus, according to hypothesis, the associated abnormality in spatial representations. We used chronically implanted high-density tetrodes to record the spatial firing properties of CA3 and CA1 units during animal exploration for food in familiar and novel environments. Aged CA3 place cells have higher firing rates, larger place fields, less spatial information content, and respond less to a change from a familiar to a novel environment than young CA3 cells. We also find that the combination of levetiracetam (LEV) + valproic acid (VPA), previously shown to act as a cognitive enhancer in tests of spatial memory, attenuate CA3 place cell firing rates, reduce place field area, and increase spatial information content in aged but not young adult rats. This is consistent with drug enhancing the specificity of neuronal firing with respect to spatial location. Contrary to expectation, however, LEV + VPA reduces place cell discrimination between novel and familiar environments, i.e., spatial correlations increase, independent of age even though drug enhances performance in cognitive tasks. The results demonstrate that spatial information content, or the number of bits of information encoded per action potential, may be the key correlate for enhancement of spatial memory by LEV + VPA.

Download full-text PDF

Source
http://dx.doi.org/10.1002/hipo.22474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4633399PMC

Still can't find the full text of the article?

We can help you send a request to the authors directly.
December 2015
48 Reads
8 Citations
4.162 Impact Factor

Publication Analysis

Top Keywords

spatial content
16
spatial
13
ca3 place
12
spatial memory
12
place cells
8
reduces place
8
field area
8
place field
8
ca3 ca1
8
spatial firing
8
spatial representations
8
familiar novel
8
firing rates
8
content aged
8
place cell
8
ca3
8
place
7
firing
5
aged
5
potential key
4

Altmetric Statistics

Similar Publications