Date of Degree
Behavioral Neurobiology | Cognitive Neuroscience | Molecular and Cellular Neuroscience | Systems Neuroscience
Startle, Prepulse Inhibition, Goldfish, Serotonin, Potassium Channels, Cortisol
Sensorimotor gating, or prepulse inhibition (PPI), attenuates the startle response during sensory processing by limiting sensory input to the startle circuit. In the goldfish startle circuit, a single action potential in the Mauthner-cell (M-cell) triggers the startle response. PPI in the M-cell is mediated by multiple post-synaptic mechanisms, including the activation of a tonic, shunting inhibition as well as a voltage-sensitive conductance, both of which briefly reduce M-cell excitability. However, the specific channels and pathways that modulate PPI are not fully known. This work further characterizes the post-synaptic conductances that mediate PPI by blocking voltage-gated and inward-rectifying potassium channels, antagonizing serotonin subtype receptors, and administering the stress hormone cortisol.
Chapter 2 characterizes the involvement of potassium conductances in sound-evoked inhibition associated with PPI. During PPI, the M-cell activates inhibitory conductances that may be potassium-related, although this has not been directly shown. We found that administration of an inward-rectifying G-protein gated potassium channel blocker interferes with PPI. In contrast, blocking a different potassium conductance, the voltage-gated potassium channel Kv1.1, attenuates an inhibitory tone in the absence of sound but PPI-related inhibition remains present. These potassium conductances contribute to shared and distinct components of sensory processing that reflect the interaction between membrane properties that are active passively and those that become active during sensory processing.
Chapter 3 describes how stress may affect sensory processing in M-cell startle circuit. We found that the steroid hormone cortisol inactivates a voltage-sensitive conductance, thereby increasing input resistance and M-cell excitability. Inactivation of this cortisol-sensitive conductance occurs in conjunction with a reduction in auditory-evoked feedforward inhibition. PPI, however, is unaffected by cortisol. Together, cortisol increased responsiveness to auditory inputs without interfering with the conductances that mediate PPI. Given cortisol’s role in the response to environmental stressors and the importance of rapid escape behavior in fish, this mechanism provides a cellular mechanism by which goldfish can adapt and respond to stressful situations without sacrificing the potential benefits of PPI associated with sensory integration.
Chapter 4 describes how serotonin 5a receptor subtype (5-HT5a) antagonists attenuate M-cell excitability while having no effect on the cellular mechanisms that mediate PPI. The reduction in M-cell excitability by 5-HT5a antagonists is mediated by the activation of a conductance, presumably chloride. In behavior, startle probability was attenuated overall. Surprisingly, the decrease in baseline excitability had an additive effect on PPI, which leads to an apparent enhancement in PPI at the behavioral level. These results describe how a tonic decrease in excitability can combine with evoked inhibition during PPI to produce a misleading effect on PPI in behavior.
Finally, the discussion section in Chapter 5 contextualizes our results within the broader framework of how excitation and inhibition are balanced during sensory processing to control behavior. In total, three goals were accomplished from this work. First, two voltage-sensitive potassium channel blockers were studied in relation to their effects on M-cell sensory processing and sensorimotor gating. Second, a cortisol-related mechanism for the modulation of sensory gain and startle latency was identified. Third, the functional role of 5-HT5a on startle plasticity was characterized. Together, the results of these studies provide an overview of the relationship between startle circuit hyperexcitability and sensorimotor gating as well as specific signaling pathways that mediate PPI.
Bronson, Daniel, "Post-Synaptic Mechanisms of Early and Late Prepulse Inhibition in the Goldfish" (2019). CUNY Academic Works.