Respiratory alkalosis provokes spike-wave discharges in seizure-prone rats

Hyperventilation reliably provokes seizures in patients diagnosed with absence epilepsy. Despite this predictable patient response, the mechanisms that enable hyperventilation to powerfully activate absence seizure-generating circuits remain entirely unknown. By utilizing gas exchange manipulations and optogenetics in the WAG/Rij rat, an established rodent model of absence epilepsy, we demonstrate that absence seizures are highly sensitive to arterial carbon dioxide, suggesting that seizure-generating circuits are sensitive to pH. Moreover, hyperventilation consistently activated neurons within the intralaminar nuclei of the thalamus, a structure implicated in seizure generation. We show that intralaminar thalamus also contains pH-sensitive neurons. Collectively, these observations suggest that hyperventilation activates pH-sensitive neurons of the intralaminar nuclei to provoke absence seizures.

Optical mini-stroke of thalamic networks impairs sleep stability, topography and cognition.

Modelling stroke in animals remains a challenge for translational research, especially for the infraction of small subcortical arteries. Using combined fibre optics and photothrombosis technologies, we developed a novel model of optically-induced infarcts (Opto-STROKE). Combining our model with electrophysiological recordings in freely-behaving mice, we studied early and late consequent patho-physiological changes in the dynamics of sleep-wake circuits and cognitive performance. Here, focusing on inducing Opto-STROKE lesions in the intralaminar thalamus (IL), which in humans cause severe impairments of arousal, cognition, and affective symptoms, our model recapitulated important deficits on sleep disorders presented in humans including arousal instability, concurrent to an augmented slow-wave activity and a reduction gamma power bands during wakefulness. Moreover, during NREM sleep, spindle density was decreased and topographically shifted to frontal cortices when compared to control animals. Remarkably, gamma power and spindle density were correlated with decreased pain threshold and impaired prefrontal cortex- dependent working memory in Opto-STROKE mice relative to controls. Collectively, our combined method influences both anatomical and functional outcomes of the classical stroke procedures and offers new insights on the fundamental role of the media thalamus as a hub for the regulation of both sleep-wake architecture and cognition.

Respiratory Alkalosis Provokes Spike-Wave Discharges in Seizure- Prone Rats

Hyperventilation reliably provokes seizures in patients diagnosed with absence epilepsy. Despite this predictable patient response, the mechanisms that enable hyperventilation to powerfully activate absence seizure-generating circuits remain entirely unknown. Using the WAG/Rij rat, an established rodent model of absence epilepsy, we demonstrate that absence seizures are highly sensitive to arterial carbon dioxide, suggesting that seizure-generating circuits are sensitive to pH. Moreover, hyperventilation consistently activated neurons within the intralaminar nuclei of the thalamus, a structure implicated in seizure generation. We show that intralaminar thalamus also contains pH-sensitive neurons. Collectively, these observations suggest that hyperventilation activates pH-sensitive neurons of the intralaminar nuclei to provoke absence seizures.

Rostral Intralaminar Thalamus Engagement in Cognition and Behavior

The thalamic rostral intralaminar nuclei (rILN) are a contiguous band of neurons that include the central medial, paracentral, and central lateral nuclei. The rILN differ from both thalamic relay nuclei, such as the lateral geniculate nucleus, and caudal intralaminar nuclei, such as the parafascicular nucleus, in afferent and efferent connectivity as well as physiological and synaptic properties. rILN activity is associated with a range of neural functions and behaviors, including arousal, pain, executive function, and action control. Here, we review this evidence supporting a role for the rILN in integrating arousal, executive and motor feedback information. In light of rILN projections out to the striatum, amygdala, and sensory as well as executive cortices, we propose that such a function enables the rILN to modulate cognitive and motor resources to meet task-dependent behavioral engagement demands.

Neural circuitry for maternal oxytocin release induced by infant cries

SummaryOxytocin is a neuropeptide important for maternal physiology and childcare, including parturition and milk ejection during nursing. Suckling triggers oxytocin release, but other sensory cues- specifically infant cries- can elevate oxytocin levels in new human mothers, indicating that cries can activate hypothalamic oxytocin neurons. Here we describe a neural circuit routing auditory information about infant vocalizations to the oxytocin system of the mouse brain. We performed in vivo electrophysiological recordings and photometry from identified oxytocin neurons in awake maternal mice presented with pup calls. We found that oxytocin neurons responded to pup vocalizations via input from the posterior intralaminar thalamus, and repetitive thalamic stimulation induced lasting disinhibition of oxytocin neurons. Suppression of this pathway impaired maternal behavior and playing pup calls led to central oxytocin release in vivo. This circuit provides a mechanism for transforming acoustic input into hormonal output to ensure modulation of brain state required for successful parenting.