Plasticity of the Nervous System

The nervous system has the ability to change over the life of an organism. This allows organisms from invertebrates to mammals to learn and have memory. Cellular mechanisms underlying these complex modifications include modifications that affect the synaptic strength of neuronal connections, such as long term potentiation (LTP), long term depression (LTD), facilitation, and synaptic depression.
Preparation: These mechanisms can be studied using the goldfish (Carassius auratus) as a model. In particular, the Mauthner cell (M-cell ) which is a key neuron involved in the startle reflex avoidance behavior can be used to study LTP, synaptic depression, as well as additional work on neurotransmitter release and inhibition (Figure 1 shows axons in the brainstem). Figure 2 shows the circuitry of the M-cell. The cell is identifiable through electrophysiological recordings and morphology and studies can be done in vivo.

The lab is interested in factors involved in the regulation of the synaptic connections between neurons. We are studying paired pulse depression, a short term (msec) depression of synaptic strength. In a recent paper (Waldeck et al. 2000) we show evidence that depletion of neurotransmitter, the mechanism long thought to explain depression, does not explain depression in this preparation. We suggest that some other factor is involved.

Future experiments:
We will look at neurotransmitter release during alterations in calcium concentration and also during blockers of various secretory proteins which may be involved in neurotransmitter release. Quantal analysis can be used to help determine if the mechanism is pre-synaptic or post synaptic. We are in the process (with a collaboration with Don Faber, Albert Einstein Medical University) to determine this using a Monte Carlo simulation to determine the probability of release (p) as well as the number of release sites (n), and the size of the quanta (q). We are also investigating the kinetics of release by examining the decay times of miniature excitatory postsynaptic synaptic potentials (mEPSPs).

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