RESEARCH
Issues
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.
Figure 1: Mauthner axons injected with fluorescent dyes
(red), rostral right.
Figure 2 neural circuitry and dye injection of Mauthner axon.
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).
Regeneration of the Nervous
System
The central nervous system of mammalian systems does not regenerate, however non-mammalian systems such as axons of the optic nerve of the frog and fish and the spinal cord of the fish do show regeneration. Using the goldfish preparation as explained above, we are studying this process. After crushing the rostral spinal cord, fish are unable to swim or do a startle reflex but with time both responses recover. Specifically we are focusing on physiological aspects of synapses that are indirectly affected by crushing the spinal cord, as well as determining which cells are associated with functional recovery of swimming and the startle reflex.
Figure 3: One day after spinal cord crush. (rostral left)
Figure 4: Five weeks after spinal cord crush. (rostral left)
Future experiments:
Use of neurotrophins to promote and improve axon guidance of regenerating axons, and examination of the molecular mechanism of the regeneration during the stages of re-growth.
Neural Basis of Behavior
The frog (Rana pipiens) is an excellent preparation to study visually guided behavior. Prey capture and avoidance behavior. These behaviors appear to have separate underlying neural circuits since lesions of the optic chiasm only affect avoidance behavior and not prey catching (Waldeck et al. 1995).
We would like to determine what these systems are by eliminating the prey catching and saving the avoidance behavior.
The lab is also interested in the function and anatomy of the frog M-cell. The M –cell makes sense in the developmental tadpole as a swimmer, but what is its function in the non-swimming adult frog?
PUBLICATIONS
Hsu, F.C., Waldeck, R., Faber, D.S., and S.S. Smith. Neurosteroid effects on GABAergic synaptic plasticity in hippocampus. J. Neurophysiology 89: 1929-1940. (2003)
Rich, M.M., Waldeck, R.F.,
Waldeck, R.F., Pereda, A., and D.S. Faber. Properties and plasticity of paired-pulse depression at a central synapse. J Neuroscience 20: 5312-5320. (2000)
Faber, D.S., Waldeck, R.F., and A. Pereda. Synaptic depression at an identified central synapse: evidence for different constraints on evoked and spontaneous quanta. In, “Central Synapses: Quantal Mechanisms and Plasticity” Eds. D.S. Faber, S.J. Redman, S.M. Thompson and J.S. Altman. HFSP, Strasburg, 1998.
Pinter, M.J., Waldeck, R.F., Cope, T.C., and L.C. Cork. Effects of 4 - aminopyridine on muscle and motor unit force in canine motor neuron disease. J. Neuroscience 17: 4500-4507. (1997)
Weber, B., Waldeck, R.F., and E.R. Gruberg. Seeing beyond the midline: the role of the contralateral isthmotectal projection in the leopard frog. Visual Neuroscience 13: 467-476. 1996.
Itoh, Y., Waldeck, R.F., Tessler, A. and M.J. Pinter. Regenerated dorsal root fibers form functional synapses in embryonic spinal cord transplants. J. Neurophysiology 76: 1236-1245. (1996)
Waldeck, R.F., Murphy, E.H., and Pinter, M.J. Properties of motor units following self-reinnervation of the cat superior oblique muscle. J. Neurophysiology 74: 2309-2318. (1995)
Waldeck, R.F. and Gruberg, E.R. Studies on the optic chiasm of the leopard frog. I Selective loss of visually elicited avoidance behavior after optic chiasm hemisection. Brain, Behav. Evol. 46:64-94. (1995)
Waldeck, R.F. and Gruberg, E.R. Regrowth of optic fibers and behavioral recovery after optic
chiasm transection. Exp. Neurol.
132: 229-238. (1995)
Tsai, J., Waldeck, R.F., and Gruberg, E.R. Studies on the optic chiasm of the leopard frog. II. Organization of retinotectal fibers in the optic chaism. Brain Behav. Evol. 46: 95-107. (1995)
Pinter, M.J., Waldeck, R.F., Wallace, N.,
and
Waldeck, R.F. and Gruberg, E.R. Optic chiasm and the parsing of visual information in frogs. In: “Visual Structures and Integrated Functions.” J.A. Arbib and J.-P. Ewert (eds.) (1991)
Gruberg, E.R., Wallace, M. and R. Waldeck. Relationship between isthmotectal fibers and other tectopetal systems in the leopard frog. J. Comp. Neurol. 288: 39-50. (1989)
ABSTRACTS
Waldeck, R.F. and L. Sheypuk. Basis of recovery of motor behavior in goldfish. Soc. Neurosci. Abstr. (2003)
F. –C. Hsu, Waldeck, R.F., Faber, D.S., and S.S. Smith. Estrous hormones alter the kinetics of miniature IPSCs of pyramidal cells in CA1 hippocampus. Soc. Neurosci. Abstr. 25:491.5 1999.
D.S. Faber and R.F. Waldeck. Altered kinetics of transmitter release during synaptic depression. Soc. Neurosci. Abstr. 25:187.15 1999.
Waldeck, R.F. and D.S. Faber. Presynaptic Ca2+ injections increase synaptic transmission and decrease synaptic depression at a fast central synapse. Soc. Neurosci. Abstr. 23: 887.17, 1997.
Battisti, W.P., Bozek, K., Waldeck, R.F., Lewis, C., Faber, D.S. and M. Murray. Extracellular matrix molecules in the goldfish spinal cord and their relation to regenerating Mauthner cell axons. Soc. Neurosci. Abstr. 23: 676.15, 1997.
Waldeck, R.F. , Pinter, M.J., Cope, T.C., and L.C. Cork. Effects of 4 - aminopyridine on muscle and motor unit force in canine motor neuron disease. Soc. Neurosci. Abstr. 1996.
Waldeck, R.F., Pereda, A., and Faber, D.S. Does depletion account for paired pulse depression at a fast synapse? Soc. Neurosci. Abstr., 1995.
Faber, D.S., Waldeck, R.F., and Pereda, A. Multiple modes of transmitter release at a fast synapse. Soc. Neurosci. Abstr., 1995.
Waldeck, R.F., Murphy, E.H. and Pinter, M.J. Physiological characteristics of trochlear motoneurons following reinnervation of cat extraocular muscle. Soc. Neurosci. Abstr. 20:25. 1994.
Iannuzzeli, P.G., Murray, M., Waldeck, R. , Pinter, M.J., and Murphy, E.H. Anomalous nonmyelinated branches of axotomized trochlear motor neurons are eliminated in long term regenerated trochlear nerves. FASEB Abstracts vol.9, submitted, 1995.
Waldeck, R.F. and Gruberg, E.R. Abnormal recovery of responses to visually presented prey and looming stimuli after transection of the optic chiasm in Rana pipiens. Soc. Neurosci. Abstr. 18:1310. 1992.
Waldeck, R.F., Tsai, J., and Gruberg, E.R. Organization of retinotectal fibers in the optic chiasm of Rana pipien. Soc. Neurosci. Abstr. 17:111. 1991.
Waldeck, R.F. and Gruberg, E.R. Prey catching is spared after hemisection of the optic chiasm in the frog. Soc. Neurosci. Abstr. 15: 460. 1989.
Gruberg, E.R., Wallace, M. T., Waldeck, R.F. Relationship between isthmotectal and retinotectal fibers in the frog, Rana pipiens. Soc. Neurosci. Abstr. 13:432. 1987.