Information from sensory inputs converge in the thalamus before passing on to the cerebral cortex. As the last subcortical relay station before these inputs reach the cortex, the thalamus plays an important role in the processing and gating of sensory information. The rapid nature of information processing requires that incoming sensory information be modulated or altered in the thalamus on a time scale of microseconds to milliseconds. Mechanisms by which this dynamic information gating occurs is still unclear. One hypothesis is that incoming sensory information can be rapidly modulated through short-tern synaptic plasticity. To test this hypothesis, I will examine the mechanisms underlying synaptic plasticity at a prototypical thalamic synapse, the retinogeniculate connection. I have developed a brain slice preparation of the lateral geniculate nucleus that allows me to monitor both presynaptic and postsynaptic activity at the retinogeniculate synapse. A combination of optical and electrophysiological techniques is used to measure presynaptic calcium influx and the synaptic response of the postsynaptic geniculate neuron. Using this preparation, I demonstrate a marked change in the strength and connectivity of this synapse during development. Further studies will examine the effects of neuromodulators and regular trains of stimuli on presynaptic calcium and synaptic strength. Once the underlying mechanisms of short-term plasticity are characterized, stimulation patterns mimicking retinal ganglion cell activity will be used to evaluate how information is encoded into the retinal firing patterns. In addition, the response to firing patterns will be compared over development to determine whether the translation of sensory information differs between young and old animals. By studying how these synapses encode and translate different firing patterns into neurotransmitter release, the mechanisms regulating the role of the thalamus as a dynamic information filter will be identified. Understanding these mechanisms would aid in the rational development of therapies for aberrant thalamic processes such as sleep disorders and generalized seizures.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08NS002056-06
Application #
6529060
Study Section
NST-2 Subcommittee (NST)
Program Officer
Talley, Edmund M
Project Start
1998-09-01
Project End
2003-08-31
Budget Start
2002-09-01
Budget End
2003-08-31
Support Year
6
Fiscal Year
2002
Total Cost
$125,820
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
Seeburg, Daniel P; Liu, Xiaojin; Chen, Chinfei (2004) Frequency-dependent modulation of retinogeniculate transmission by serotonin. J Neurosci 24:10950-62
Chen, Chinfei; Regehr, Wade G (2003) Presynaptic modulation of the retinogeniculate synapse. J Neurosci 23:3130-5
Chen, Chinfei; Blitz, Dawn M; Regehr, Wade G (2002) Contributions of receptor desensitization and saturation to plasticity at the retinogeniculate synapse. Neuron 33:779-88
Chen, C; Regehr, W G (2000) Developmental remodeling of the retinogeniculate synapse. Neuron 28:955-66
Chen, C; Regehr, W G (1999) Contributions of residual calcium to fast synaptic transmission. J Neurosci 19:6257-66