In the rodent hippocampus, synapses between CA3 and CA1 pyramidal cells share two key properties: 1) their synaptic strength is modifiable by NMDA receptor dependent long-term potentiation (LTP) and depression (LTD);2) the activity of many CA3 and CA1 pyramidal cells is location specific in that such "place cells" discharge rapidly only when a rodent's head is in an environment-specific region called the "firing field". The combination of synaptic plasticity and location-specific firing suggests that important spatial information about the environment may be encoded in the strength of pyramidal cell synapses. For instance, theories of spatial mapping based on spike-timing dependent plasticity rules suggest that directional vectors can be encoded in synapses (Blum and Abbott, 1996;Bush et al., 2010). Another example is the graph theory of spatial mapping, which posits that synapses connecting cell pairs with coincident or overlapping fields should strengthen since the two cells will fire together whereas synapses connecting cell pairs with separated fields should remain weak since the two cells will fire only at different times (Muller et al., 1996). A recent report y Isaac and col. (2009) has provided with exciting evidence that strengthens the link between place cell spiking activity and synaptic function, demonstrating that distance is encoded in the strength of individual synapses. In their studies, Isaac and col. used a "dual stimulation" method where the spiking activity of one place cell is used to stimulate the presynaptic Shaffer collatera input to a CA1 pyramidal cell in a hippocampal slice. At the same time, the activity of a second, simultaneously recorded place cell is used to evoke discharge of the patch-clamped postsynaptic CA1 cell. In spite of these advances, there still is unclear what precise synaptic encoding give rise to plastic changes in synapses of place cells. We will utilize the Isaac and col. (2009) method to identify 1) what kind of synaptic encoding govern the magnitude of strengthening or weakening of plastic synapses subjected to place cell firing stimulation, and, 2) how this synaptic encoding relates to navigational behavior. The significance of this project is two-fold. On one hand it is an empirical exploration of how plastic synapses are modified by location-specific firing, the most powerful signal generated by primary cells in the hippocampus. On the other hand, it will provide first order tests of theoretical models that pose synaptic plasticity mechanisms underlie cognitive mapping.

Public Health Relevance

The human hippocampus is a key brain area for the processing of spatial, episodic (autobiographical) and semantic (factual) memory - failures of hippocampal function are implicated in Alzheimer's disease as well as other cognitive disorders. Our proposed research is aimed at understanding a fundamental function of the hippocampus of laboratory rats, namely, how a representation of the world is formed in the brain. The goal is enhancing the knowledge of the processes and mechanisms whose malfunction underlie increasingly common cognitive disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Small Research Grants (R03)
Project #
1R03NS081625-01A1
Application #
8637582
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Talley, Edmund M
Project Start
2013-09-15
Project End
2015-08-31
Budget Start
2013-09-15
Budget End
2014-08-31
Support Year
1
Fiscal Year
2013
Total Cost
$80,000
Indirect Cost
$30,000
Name
Suny Downstate Medical Center
Department
Pathology
Type
Schools of Medicine
DUNS #
040796328
City
Brooklyn
State
NY
Country
United States
Zip Code
11203