Yuri Geinisman
Title: Research Professor
Research area: Synaptic substrates of age-related memory deficits
Degree: M.D., First Moscow Medical School; Ph.D., USSR Academy of Medical Sciences
Voice: 312.503.8389
Fax: 312.503.7912
e-mail: yurig@northwestern.edu

Detailed research description:
Loss of memory, especially for newly acquired information, is one of the hallmarks of normal aging. Yet, it has long been noted that some individuals retain remarkably intact memory even at advanced chronological age. An important and still unresolved problem in the neurobiology of aging is how to explain why memory is preserved in some aged individuals and lost or impaired in others. Ongoing experiments were designed to investigate this problem by testing the hypotheses that memory deficits typical of the majority of aged individuals are due to a loss of synapses and/or to an increase in the proportion of silent synapses in pertinent brain regions. Young adult and old rats are characterized behaviorally and electrophysiologically (this part of work is being done in collaboration with Dr. John F. Disterhoft). Two behavioral tasks, the Morris water maze and trace eyeblink conditioning, are used to separate old rats into memory-impaired and memory-intact subgroups based on the presence or absence of memory deficits as compared with young adults. The structural integrity of the hippocampus is a prerequisite for successful performance of animals on these tasks. Electrophysiologically, the efficacy of synaptic transmission is evaluated in two hippocampal subregions (CA1 and dentate gyrus) with the aid of field potential recordings in vivo. At the electron microscopic level, unbiased estimates of the total number of synapses in these hippocampal subregions are obtained, using sampling and counting procedures of modern stereology. The results will show whether old animals with marked impairments of hippocampus-dependent memory function are the ones that exhibit a loss of hippocampal synapses and a decline in efficacy of synaptic transmission. Additionally, immunocytochemical techniques will be used to estimate the proportion of hippocampal synapses that contain NMDA receptors, but lack AMPA receptors. Although these synapses appear morphologically normal, they cannot evoke postsynaptic responses and are, therefore, silent. It will be determined if the number of silent synapses is increased in old memory-deficient animals. Such data are essential for a better understanding of the cellular mechanisms that underlie deficits in learning and memory typical of normal aging. Moreover, the data may be useful for designing preventive measures to make aging "successful".

Representative publications:

Geinisman, Y., L. deToledo-Morrell, F. Morrell and R.E.
  Heller. 1995. Hippocampal markers of age-related
  memory dysfunction: behavioral, electrophysiological and
  morphological perspectives. Prog. Neurobiol. 45:223-252.

Geinisman, Y., H.J.G. Gundersen, E. Van der Zee and
  M.J. West. 1996. Unbiased stereological estimation of
  the total number of synapses in a brain region.
  J. Neurocytol. 25:805-819.

Geinisman, Y. 1999. Age-related decline in memory function:
  is it associated with a loss of synapses? Neurobiol.
  Aging 20:353-356.

Geinisman, Y., J.F. Disterhoft, H.J.G. Gundersen, M.D.
  McEchron, I.S. Persina, J.M. Power, E.A. Van der
  Zee and M.J. West. 2000. Remodeling of hippocampal
  synapses following hippocampus-dependent associative
  learning. J. Comp. Neurol. 417:49-59.

Geinisman, Y. 2000. Structural synaptic modifications
  associated with hippocampal LTP and behavioral learning.
  Cereb. Cortex 10:952-962.