Optogenetic inhibition of Purkinje cell activity reveals cerebellar control of blood pressure during postural alterations in anesthetized rats

Tsubota, Tadashi; Ohashi, Yohei; Tamura, Keita; Miyashita, Yasushi

doi:10.1016/j.neuroscience.2012.03.014

Cited by 17 publications

(15 citation statements)

References 28 publications

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“…When the amplitude of the Desired BP fell in the simulations, there was an initiation of a reduction in both BP and HR, leading to a simulated vasovagal response by the model. Where such a signal arises is unknown, but it could come from the interaction of the uvula with the VSR and the cardiovascular system (52). Direct projections extend from the uvula to the otolithic portions of the Vestibular Nuclei to the parabrachial nuclei and the Nucleus Tractus Solitarius (NTS) that receive the input from the baroreflex receptors (53–57).…”

Section: Discussionmentioning

confidence: 99%

“…Direct projections extend from the uvula to the otolithic portions of the Vestibular Nuclei to the parabrachial nuclei and the Nucleus Tractus Solitarius (NTS) that receive the input from the baroreflex receptors (53–57). There is also a disynaptic projection from the uvula to NTS that could control baroreflex sensitivity (29, 52, 58–61). If this is correct, then projections from the uvula could be the critical input to control susceptibility to sympathetic activation of syncope, regardless of whether it arises from direct activation of the VSR or from one of the many other causes of vasovagal syncope that project through the parabrachial nuclei.…”

Section: Discussionmentioning

confidence: 99%

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Vestibular Activation Habituates the Vasovagal Response in the Rat

et al. 2017

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Vasovagal syncope is a significant medical problem without effective therapy, postulated to be related to a collapse of baroreflex function. While some studies have shown that repeated static tilts can block vasovagal syncope, this was not found in other studies. Using anesthetized, male Long–Evans rats that were highly susceptible to generation of vasovagal responses, we found that repeated activation of the vestibulosympathetic reflex (VSR) with ±2 and ±3 mA, 0.025 Hz sinusoidal galvanic vestibular stimulation (sGVS) caused incremental changes in blood pressure (BP) and heart rate (HR) that blocked further generation of vasovagal responses. Initially, BP and HR fell ≈20–50 mmHg and ≈20–50 beats/min (bpm) into a vasovagal response when stimulated with Sgv\S in susceptible rats. As the rats were continually stimulated, HR initially rose to counteract the fall in BP; then the increase in HR became more substantial and long lasting, effectively opposing the fall in BP. Finally, the vestibular stimuli simply caused an increase in BP, the normal sequence following activation of the VSR. Concurrently, habituation caused disappearance of the low-frequency (0.025 and 0.05 Hz) oscillations in BP and HR that must be present when vasovagal responses are induced. Habituation also produced significant increases in baroreflex sensitivity (p < 0.001). Thus, repeated low-frequency activation of the VSR resulted in a reduction and loss of susceptibility to development of vasovagal responses in rats that were previously highly susceptible. We posit that reactivation of the baroreflex, which is depressed by anesthesia and the disappearance of low-frequency oscillations in BP and HR are likely to be critically involved in producing resistance to the development of vasovagal responses. SGVS has been widely used to activate muscle sympathetic nerve activity in humans and is safe and well tolerated. Potentially, it could be used to produce similar habituation of vasovagal syncope in humans.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Vestibular Activation Habituates the Vasovagal Response in the Rat

et al. 2017

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“…The multiplexed usage of single neurons to control multiple targets has behavioral as well as physiological consequences. For example, inhibition of serotonin neurons or Purkinje cell activity via optogenetic or chemogenetic means can alter core body temperature or blood pressure (Ray et al 2011;Tsubota et al 2012), revealing new functions not widely thought of as being associated with these cell types.…”

Section: Network-level Side Effectsmentioning

confidence: 99%

Principles of designing interpretable optogenetic behavior experiments

2015

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Over the last decade, there has been much excitement about the use of optogenetic tools to test whether specific cells, regions, and projection pathways are necessary or sufficient for initiating, sustaining, or altering behavior. However, the use of such tools can result in side effects that can complicate experimental design or interpretation. The presence of optogenetic proteins in cells, the effects of heat and light, and the activity of specific ions conducted by optogenetic proteins can result in cellular side effects. At the network level, activation or silencing of defined neural populations can alter the physiology of local or distant circuits, sometimes in undesired ways. We discuss how, in order to design interpretable behavioral experiments using optogenetics, one can understand, and control for, these potential confounds.

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“…More recently, specific optogenetic stimulation of cerebellar Purkinje cells in the uvula (lobule IX of the posterior vermis), was also shown to decrease blood pressure in anesthetized rats, whereas optogenetic inhibition of the same area led to increases in blood pressure (Tsubota et al, 2011). These responses are thought to be related to the role of the vermis in maintaining blood pressure during upright posture (Holmes et al, 2002;Tsubota et al, 2012). The vermis also projects profusely to the vestibular nuclei, and the profound autonomic responses to vestibular stimulation (El Sayed et al, 2012) indicate that the vestibular nuclei must have a direct and very potent input into the autonomic control system.…”

Section: Cerebellummentioning

confidence: 99%