Rationale: Recent work in Sudden Unexpected Death in Epilepsy (SUDEP) has suggested failures of central respiratory control.
1 We have previously investigated ictal rodent deaths in response to an apneic stimulus, including single microwire recordings in the respiratory brainstem. In this work we expand our recordings to hundreds of channels. We are especially interested in gasp formation in the brainstem in response to these stimuli.
Methods: We anesthetize Long Evans rats with urethane. We record diaphragmatic electromyography, diaphragm deflection via a pressure pillow, electrocardiography, nasal airflow via thermocouple, and neural probe data. We insert a Neuropixel probe into the brainstem, following a tract to hit the solitary nucleus (SolN), parvicellular reticular nucleus (PCRt), and ventral respiratory column (VRC). The probe is inserted to a depth of 9 mm. We deliver approximately 0.5 mL of cold water via a cannula in the nares to initiate the diving reflex. We initiate seizures with kainate and repeat reflexes until death.
Results: Probe data yield some single units and some population activity. For a preictal gasp (i.e., first, strong inspiratory effort observed after an apnea) we observe large population bursts. We also observe some single units which change firing rate with gasps – some (PCRt, SolN) increase firing rate, while others (SolN, VRC) decrease firing rate. Population activity and measures of respiratory output (diaphragm, airflow measures) are 100% correlated. In seizure, population bursts become very decorrelated from respiratory output. Some single units follow the population bursts, while others continue to follow respiratory output. See Figures. PCRt single units can follow either, while SolN and VRC only follow true respiratory output. Population bursts match jaw movements in the animal and are possibly swallow-related.
Conclusions: Gasps are strongly linked with autoresuscitation and survival from respiratory crisis.
2 The swallowing reflex is strongly implicated in gasp and respiratory defense mechanisms.
3. Our data may suggest that an aberrant swallowing reflex is suppressing or competing with normal pro-eupnea gasping drive during seizure, but not preictally. Further investigation into the swallow-gasp reflex dynamics suggested here may yield insight into the SUDEP mechanism.
References:
1 R. K. Sainju
et al.,
Epilepsia, 2019.
2 D. Gozal
et al.,
J of Applied Physiol, 2002.
3 T. Nishino,
Front Physiol, 2013.
These experiments comply with ARRIVE guidelines, the NIH CULA, and are approved by the Johns Hopkins ACUC.
Funding:
NIH NS119390