Physiology Department Research Larry Grover, Ph.D. Associate Professor Phone: 304/696-7328 Fax: 304/696-7381 E-Mail: grover@marshall.edu

RESEARCH INTERESTS:

• Neural basis of learning and memory
• Synaptic plasticity
• Excitatory and inhibitory amino acid neurotransmission
• Neurotransmitter and second messenger regulation of neuronal excitability and synaptic transmission
• Synaptic physiology of the hippocampus

CURRENT RESEARCH PROJECTS:

• Signaling Pathways in NMDA-receptor Independent Long-Term Potentiation (LTP)
• Modulation of Hippocampal LTP by Rapid Eye Movement (REM) Sleep Deprivation

Long-Term Potentiation (LTP)

• LTP is a long-lasting (hours to days) increase in the strength of a synapse. LTP is caused by brief (seconds or less) periods of high frequncy activation of the synapse.
  

  Example of LTP. Membrane potentials were recorded from a pyramidal neuron in the CA1 area of the rat hippocampus. Presynaptic axons were stimulated, so that an Excitatory Postsynaptic Potential (EPSP) could be recorded ("before LTP", shown above). The presynaptic axons were then stimulated for a brief period of time (0.5 sec) at a high frequency (200 Hz), to induce LTP. After high frequency stimulation, the excitatory synapses were strengthened, as revealed by the larger EPSP ("during LTP", above).
  

• LTP is triggered by a brief increase in calcium concentration in the postsynaptic neuron. This increase in intracellular calcium is caused by calcium influx through NMDA-type glutamate receptors, or voltage-gated calcium channels. If the postsynaptic neuron is filled with a calcium chelator, the free calcium concentration cannot rise, and LTP is prevented.
  

  Example. The recording electrode was used to load this neuron with a calcium chelator (BAPTA, see Grover & Teyler, 1990). High frequency stimulation did not cause LTP in this neuron.

• The rise in intracellular calcium concentration activates additional processes in the postsynaptic neuron which lead to long-lasting changes in the function of the synapse.

  Model of an excitatory synapse before LTP. Glutamate is released from the presynaptic terminal into the synaptic cleft, where it binds to and activates glutamate receptors in the postsynaptic membrane (modified from Grover, 1998).
  

   

  A rise in caclium concentration in the postsynaptic neuron can increase the number of functional glutamate receptors in the postsynaptic membrane. As a result, glutamate released from the presynaptic terminal activates a greater number of postsynaptic receptors, causing a larger postsynaptic response (modified from Grover, 1998).
  

  
  Postsynaptic calcium also stimulates the formation of nitric oxide (NO), which can diffuse through cell membranes. NO acts on the presynaptic terminal to increase the release of glutamate. The increase in glutamate release allows a greater fraction of the postsynaptic glutamate receptors to be activated, causing a larger postsynaptic response (modified from Grover, 1998).

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