ORCID
http://orcid.org/0000-0001-6969-5478
Date of Award
Spring 5-15-2023
Degree Name
Doctor of Philosophy (PhD)
Degree Type
Dissertation
Abstract
A fundamental question in neuroscience is: how does a sensory system optimize detection of behaviorally relevant stimuli, when those stimuli and the sensory environment are constantly changing? Spike-timing-dependent plasticity (STDP), in which synapse strength changes based on the relative timing of pre- and post-synaptic spiking, has been implicated in changes in neuronal connectivity thought to underlie learning and memory. Synaptic strength changes caused by STDP have been shown in optic tectum, visual cortex, hippocampus, and other brain regions in vitro across many organisms like fish, frogs, and mice. Although it is possible that STDP mechanisms underlie changes in sensory neuron connectivity, the relationship between sensory stimulation and central sensory neuronal response is complex and often involves populations of neurons that differ in the timing and frequency of spiking, resulting in complex spatiotemporal patterns of synaptic input to postsynaptic neurons. The organism I studied, weakly electric fish, produce and receive electric organ discharges (EODs) used to electrolocate and communicate. Taking advantage of the electrosensory system, weakly electric fishes are a system in which spiking patterns are themselves the behaviorally relevant stimulus. Previous work showed that STDP predictably altered synaptic xi responses and inter-pulse interval tuning in vitro (Ma and Carlson, unpublished). Using whole-cell intracellular recordings to repetitively pair sensory stimulation with intracellular spiking in vivo, I manipulated the relative timing of pre- and post-synaptic spiking in central sensory neurons in awake, behaving animals. I found that STDP alters sensory responses of central electrosensory neurons in vivo but there was more variability in the changes in sensory responses in vivo relative to the in vitro changes in synaptic responses (Chapter 2). Whether the in vivo data “fit” or “did not fit” the pattern predicted by the in vitro results was correlated with variations in synaptic potential landmarks. That variations in synaptic potential landmarks correlated with deviations from the pattern shown in vitro results suggest that whether the data “fit” or “did not fit” the in vitro hypothesis is influenced by polysynaptic activity, including inhibitory interneurons (Chapter 2). I now asked whether STDP could alter sensory tuning to behaviorally relevant stimuli in vivo. Using whole-cell intracellular recordings, I recorded postsynaptic potential responses to two different sensory stimuli before and after pairing postsynaptic spiking with only one of those sensory stimuli. I found that some in vivo responses followed the pattern predicted by STDP sensory tuning experiments done in vitro and some in vivo responses that did not. Whether the in vivo sensory tuning data “fit” or “did not fit” the pattern predicted by the in vitro sensory tuning changes was correlated with variations in synaptic potential landmarks. That variations in the synaptic potential landmarks correlated with differences in the in vitro and in vivo sensory tuning suggest that whether the in vivo tuning results did or did not “fit” the in vitro tuning prediction is influenced by polysynaptic activity, including inhibitory interneurons (Chapter 3). Next, I wanted to ask whether intrinsic network activity could alter sensory tuning based solely on the input of behaviorally relevant stimuli. Using extracellular evoked potential recordings and a freely behaving paradigm, I recorded postsynaptic potential responses and behavioral output to two xii different sensory stimuli before and after repeating only one of those sensory stimuli, with no pairing of postsynaptic spiking. I did not find any significant differences in the evoked potentials or behavior as a result of repetition of a sensory stimulus (Chapter 4). Thus, in this dissertation I showed that STDP can alter the sensory responses of central electrosensory neurons, but that STDP rules operating at identified synapses may not drive predictable changes in sensory responses and sensory tuning at the circuit or behavioral level. In conclusion, for altering sensory tuning in adult organisms in a changing sensory environment in vivo, the role of STDP is more complex than had been predicted from previous work in vitro
Language
English (en)
Chair and Committee
Bruce Carlson
Committee Members
Steven Mennerick, Martha Bagnall, Keith Hengen, Baranidharan Raman,
Recommended Citation
Lube, Adalee, "Spike-Timing-Dependent Plasticity Alters Sensory Network Connectivity" (2023). Arts & Sciences Electronic Theses and Dissertations. 2882.
https://openscholarship.wustl.edu/art_sci_etds/2882