Short-term and long-term plasticity of hippocampal synapses
Synapses exhibit different forms of plasticity over a wide range of
time scales. We are interested in the functional roles of both
short-term and long-term activity-dependent changes in synaptic
parameters such as strength, probability of release, and time
constants of depression and facilitation. The mossy fiber synapse
provides the main feedforward input to the hippocampal CA3 region, and
it is a key example for plasticity. In close collaboration with
D. Schmitz (Charité) we will characterize this synapse and its
plasticity, and evaluate its functional role for information
processing within the hippocampus. In a similar way, the recurrent
A/C synapses in CA3 will be quantitatively described.
Spike-timing-dependent synaptic plasticity and network stability
We explore how the activity and stability (e.g. against epileptiform
activity) of a recurrent network of spiking neurons depends on its
input and on the synaptic plasticity within the network. This is of
particular importance in order to understand, for example, the
dynamics and function of the CA3 region of the hippocampus. CA3 is
characterized by strong recurrent connections, an associative
component of synaptic learning, and oscillatory activity
patterns. Often epileptiform activity has its origin in CA3. How is
the network activity stabilized? (collaboration with D. Schmitz,
Charité) A second focus of interest is the somatosensory cortex. It
has been shown that massive sensory training can lead to local
instability of cortical tissue. This functional brain illness is
called focal dystonia. Using a network model of spiking neurons, we
aim at developing stimulation strategies that can re-stabilize an
unstable network. We are also studying practical implications for
designing remedial therapies for focal dystonia (collaboration with
M.M. Merzenich, D.T. Blake, San Francisco).
Hippocampal learning of a sequence of events and the representation
of time
The hippocampus is involved in the association of a sequence of
events, where events are separated by more than a
second. Surprisingly, the learning window of spike-timing-dependent
synaptic plasticity for recurrent synapses within the CA3 region has a
width of at most 100 milliseconds. We aim at developing a model of the
CA3 region of the hippocampus that can answer the following questions:
How can the hippocampus bridge a gap of several seconds between
separate events of a sequence? How is a sequence of events represented
within the recurrent connections within the CA3 region? What is the
role of hippocampal network oscillations, such as the theta/gamma
rhythms and the sharp wave/ripple complex, for storage and retrieval?
What is the origin of phase precession (with respect to the theta
rhythm) of spiking of CA3/CA1 pyramidal cells? How can a learned
sequence be recognized? How can the information be transferred to
other cortical regions for long-term storage? (collaboration with
D. Schmitz, Charité)
Zwicker tone, tinnitus, and noise reduction in the auditory system
The Zwicker tone as a transient auditory illusion is often thought of
as a short-term tinnitus. Tinnitus, on the other hand, is a long-term
phantom percept. Tinnitus and Zwicker tone are related in that both
can be perceived as a pure tone that is generated most likely in the
central auditory system. Both can be induced by a `spectral gap' in
the auditory-nerve activity. The Zwicker tone is believed to be the
result of a short-term adaptation in the early auditory system in
order to reduce background noise. Its long-term counterpart is a
common type of tinnitus that develops over days following peripheral
hearing loss. The perceived pitch of the illusionary pure tone often
matches frequencies of the hearing loss. Central tinnitus and the
associated persistent activity in auditory brain stem nuclei might be
the result of a long-term synaptic plasticity. By incorporating
synaptic learning rules into our current network model of the Zwicker
tone (which has been developed in collaboration with L. van Hemmen,
M. Franosch, and H. Fastl) we hope to gain further insights into the
mechanism underlying the generation of tinnitus. Major goal in this
project is to develop prospects for new rehabilitation strategies.
Mapping time in the barn owl's laminar nucleus
When sound reaches one ear before the other, the brain uses the
resulting interaural time differences (ITDs) to localize the
sound. The barn owl is a nocturnal hunter and a classical model for
how we localize sound and process temporal information in
general. ITDs are translated into a place code in space in the brain
stem. Detection of these time differences depends upon two mechanisms
of general significance to neurobiology, delay lines and coincidence
detection. Incoming axons form delay lines to create maps of ITD in
nucleus laminaris. Their postsynaptic targets act as coincidence
detectors and fire maximally when the interaural time difference is
compensated for by the delay imposed by the afferent axons. Current
research is focused on models of delay-line-coincidence detector
circuit, and on the assembly of the map of sound localization during
development (collaboration with C. E. Carr and H. Wagner).