Dawn Blitz - US grants

Multifunctional neural networks underlie a variety of rhythmic behaviors and while anatomically hard-wired, they are functionally flexible. This proposal examines cellular mechanisms of flexibility in the mammalian respiratory system. One important modulator of respiration is oxygen level. In vivo, the respiratory system response to repetitive episodes of low oxygen, is a long lasting facilitation (LTF) of respiratory activity that is serotonin dependent. In this proposal: (1) I will determine if the respiratory system in the isolated rhythmic brain stem slice also expresses LTF following episodes of low oxygen. I will use whole cell patch clamp recordings to examine long term changes in activity of respiratory network and motor neurons as well as respiratory frequency. (2) I will use pharmacological techniques to determine if the LTF is serotonin dependent. (3) I will determine cellular mechanisms underlying LTF by using current and voltage clamp recordings to determine if there are changes in bursting properties, ion channels and/or synaptic transmission in respiratory network neurons. This work will increase our knowledge of respiratory network modulation, and will contribute to our understanding of disorders such as sleep apnea, since it is thought an enhancement of serotonergic drive to the respiratory system following periods of low oxygen may be a response to sleep apnea episodes.

The neural circuits, called central pattern generators (CPGs), underlying rhythmic behaviors (e.g., walking, breathing, chewing) are functionally flexible, producing multiple versions of a particular behavior (e.g., walking, running, swimming). A central goal in neuroscience is to determine how the output of a behaviorally-appropriate circuit is selected from such multifunctional circuits. Projection neurons are a major source for altering circuit output and, like most neural circuits, CPG circuits provide feedback to their projection neuron inputs. However, little is known regarding the function and modifiability of this feedback. Thus, this proposal aims to determine whether the strength of CPG feedback to projection neurons is modifiable and, if so, how such modulation alters projection neuron activity and the resulting CPG output pattern. To this end, multiple electrophysiological techniques will be utilized at the level of the projection neuron, CPG and muscle. It is anticipated that this project will provide the first demonstration of long-term modulation of CPG feedback and a cellular-level analysis of its functional consequences. It will also emphasize the under-appreciated concept that neural systems do not operate via a unidirectional flow of information, but require bidirectional communication between so called hierarchical levels. Both general principles and specific circuit mechanisms determined in the crustacean stomatogastric nervous system used in this proposal have effectively translated to other systems, including the mammalian CNS. The demonstration that circuit feedback is modifiable would open a new line of research in other systems, where feedback was not previously considered as a site of plasticity in determining CPG output. This project will provide training opportunities for graduate and undergraduate students, comprising cellular- to systems-level experimentation and analysis, including comprehensive training in electrophysiology, an experimental area in which women and other groups are particularly underrepresented. Students will have opportunities to present their work and interact with colleagues at local, national and international meetings each year.