Sensory stimulation modulates a feedback synapse. (Top) Before stimulation of sensory neurons, there was no evident synaptic current elicited in the projection neuron CPN2 during activation of the circuit feedback neuron, Int1. (Bottom) After sensory stimulation, Int1 activation elicits a large inhibitory synaptic current in CPN2. (Blitz J Neurophysiol, 2017)

Generating an appropriate behavior requires that neural circuits alter their output in response to changes in the internal (e.g. hungry vs. sated, stressed vs. calm) and external (e.g. food or predator nearby) environment. Changes in circuit output result largely from sensory input and input from other regions of the central nervous system (CNS). These inputs commonly converge onto descending modulatory projection neurons, which then integrate the incoming information and alter the intrinsic properties of individual neurons and the strength of connections among circuit neurons. We aim to identify mechanisms of integration at the level of descending inputs and determine how the resulting activity in the projection neurons selects a specific motor circuit output and thus an appropriate behavior.

Confocal image of the projection neuron MCN1 filled with Alexa 568. Swallie, Monti, Blitz PLoS One (2015)

Confocal image of the projection neuron MCN1 filled with Alexa 568. Swalllie, Monti, Blitz PLoS One (2015)

We are currently addressing these issues by determining how distinct circuit outputs are triggered by extrinsic inputs conveying different information (sensory and central nervous system), via their convergent yet distinct actions on the same projection neurons.  Transient sensory stimuli can trigger long term activation of projection neurons and their target circuits. However, little is known about the cellular mechanisms underlying this long term activation, nor is it known how such activation influences the response of projection neurons to other inputs.  Thus, one area of research involves determining the cellular mechanisms underlying long term activation of projection neurons and whether different extrinsic inputs use distinct mechanisms for long-term activation of the same projection neurons.

Synaptic plasticity differs at different muscles innervated by the same motor neuron. Stimulation of the LG motor neuron results in different dynamics of the resulting excitatory junction potentials in muscles gm6ab (top) and gm5b (bottom). Traces are overlaid for rhythmic bursts of stimulations with different inter-burst intervals. Durations (seconds) of inter-burst intervals are indicated in color code at center of figure. (Blitz, Pritchard, Latimer, Wakefield, J Exp Biol 2017).

In order to more fully understand how distinct outputs are generated, we are also investigating the role of feedback pathways.  Many circuits throughout all nervous systems provide feedback to their inputs.  However, little is known regarding the function of circuit feedback and whether it is subject to modulation.  Recently, we found that the strength of feedback synapses is indeed subject to modulation by sensory and higher order inputs.  We now aim to determine the function of circuit feedback and its modulation, in regulating projection neuron responses to sensory inputs including the consequences for motor circuit output.  An additional advantage of the STNS is the ability to work at multiple levels of a motor pathway.  We are not only able to work with identified circuit, projection and sensory neurons but also to quantify electrical and mechanical responses of identified muscles.  Therefore, we are also investigating to what extent modulation of circuit feedback results in distinct muscle responses.

Amanda Rainey using confocal microscopy to trace axons in the thoracic ganglion.

Ongoing research also includes determining the cellular and synaptic properties enabling neurons to switch between distinct oscillatory circuits, including circuits operating at distinct frequencies (e.g., respiration and vocalization, multiple cortical or hippocampal rhythms).  The small numbers of neurons in circuits in the chewing and filtering rhythms in the stomatogastric nervous system enables us to create hybrid biological-computational circuits in order to test the role(s) of individual synaptic and intrinsic currents within a functional circuit.

Listen to an extracellular nerve recording which monitors the pyloric rhythm.The pyloric rhythm is a three phase rhythm which controls the rhythmic filtering behavior of the crab foregut.

See crabs being fed.

See crab muscles disappearing. Happy Holidays!

See the teeth moving inside the crab stomach during a POC type gastric mill (chewing) rhythm.

The research in our lab is supported by the National Science Foundation, Miami University Undergraduate Research Award and Summer Scholar Programs, and the Department of Biology.

Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.

“The most exciting phrase to hear in science, the one that heralds the most discoveries, is not “Eureka!” (I found it!) but ‘That’s funny…”
― Isaac Asimov

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