Bland, B. H. | bioRxiv Science

bioRxiv2021

Basal Ganglia Responses to Electrical Stimulation of the Posterior Hypothalamic Nucleus

Electrical or chemical stimulation of the posterior hypothalamic nucleus (PH) elicits highly adaptive locomotion, demonstrating both evidence of flexibility and variety in exhibited motor behaviours. However, the neural substrates of PH stimulation elicited behavioural changes are poorly understood. The basal ganglia are postulated to be critically involved in the process of action selection in conjunction with thalamo-cortical systems. The present study examines changes in basal ganglia activities in response to the high-frequency stimulation of the PH. Under urethane anaesthesia, ensemble and single-unit recordings were obtained from the striatum (STR), globus pallidus externa (GPe), entopeduncular nucleus (EP), subthalamic nucleus (STN) and the substantia nigra pars reticulata (SNr). Upon PH stimulation, increases in firing rates were observed in the STR, GPe, and STN, a decrease was observed in the SNr and no changes were seen in the EP. The increase in spike rate in the STR and GPe was dependent on the stimulation intensity but not duration. Despite the differences in the direction of firing changes during PH stimulation, all examined areas including those not part of the basal ganglia demonstrated an elevated spiking rate upon stimulus train termination. Taking into account the known anatomical connections between the PH and the basal ganglia, it is hypothesized responses seen during PH stimulus trains are mediated through thalamic and cortical relays whereas the overall post-stimulus excitatory response is related to the impact of the PH on brainstem arousal systems.

neuroscience↗

bioRxiv2021

Activation of thalamo-cortical circuits with posterior hypothalamic nucleus deep brain stimulation

The posterior hypothalamic nucleus (PH) has extensive anatomical connections to motor, cognitive, visceral, and homeostatic areas of the brain and serves as a crucial subcortical modulator of behaviour. Previous studies have demonstrated that deep brain stimulation (DBS) of this area can lead to powerful activation of motor behaviour, overcoming two rodent models of parkinsonian akinesia by increasing neocortical excitability. However, it is unclear how the PH may mediate this increase in neocortical excitability. In the present study, we examined the role of the thalamus in the PH-DBS mediated increase in neocortical excitability. In urethane anaesthetized animals, we demonstrate that PH-DBS elicits increased spiking activity in the motor thalamus (VL) that receives direct afferents from the PH that precedes the increase in spiking activity in the corresponding motor cortex. In contrast, in the somatosensory thalamus (VPM) where PH afferents are sparse at best, PH-DBS did not elicit an increase in thalamic activity despite of a slight increase in the corresponding somatosensory cortical spiking. Current source density analyses suggest a thalamo-cortical mechanism for motor cortex activation whereas a cortico-cortical activation mechanism is involved in somatosensory cortical activation. Inactivation of the VL resulted in the abolition of motor cortex spiking despite of the persistence of desynchronized field potential activity. Collectively, these data suggest indirect orthodromic activation of PH output fibres to the thalamus mediates increased neocortical excitation, which may spread through cortico-cortical connections and lead to an increase in integrated, non-stereotypical motor behaviour.

neuroscience↗