CEREBELLAR CONTROL

OF AUTONOMIC
FUNCTION

ROCCO BRUNO
YOUNGSTOWN STATE UNIVERSITY

MENTOR: RONALD R. SEESE, M.D., PH.D.

BEDSIDE-TO-BENCH & BENCH-TO-BEDSIDE

Neuropsychiatric Disorders
• Prominent and difficult-to-treat dysautonomia
• Structural and functional abnormalities of the cerebellum
Does the cerebellum influence autonomic output?

Do cerebellar abnormalities contribute to dysautonomia?

Can the cerebellum be targeted to treat dysautonomia?

MAPPING THE
CIRCUIT

• Non-human primates
• Transneuronal transport
of Rabies Virus
 MAPPING THE
CIRCUIT
1) Immunohistochemistry

These are Purkinje Neurons!

• GABAergic Inhibitory Neurons

• Represent sole output from Cerebellar
Cortex
• Loss of these neurons is characteristic in
many neuropsychiatric disorders
• If we target remaining cells, can we
treat symptoms?
 MAPPING THE
CIRCUIT
1) Immunohistochemistry
2) Identification of
Purkinje Cells that
influence the adrenal
medulla
3) Reconstruction of the
Cerebellum
CEREBELLAR CONTROL OF AUTONOMIC
OUTPUT IS ROBUST AND DIVERSE
 SMOOSH!

Cerebellum: Anatomy | concise medical knowledge. (2022, November 21). https://www.lecturio.com/concepts/cerebellum/

Cerebellum: Anatomy | concise medical knowledge. (2022, November 21). https://www.lecturio.com/concepts/cerebellum/
 CEREBELLAR CONTROL OF AUTONOMIC
OUTPUT IS ROBUST AND DIVERSE

Which of these sites have the strongest influence over

autonomic output?
THE CEREBELLAR VERMIS HAS THE STRONGEST
INFLUENCE OVER AUTONOMIC OUTPUT
HOW DO WE ENSURE OUR MAPS ARE VALID?
COMPARING SPECIES: MARMOSET VS. CEBUS
DIRECT CONTROL IN CEBUS MONKEYS
 OUR NEXT STEPS
• What neural network is each adrenal-related
cerebellar hotspot part of?
• Motor network?
• Physiologic response (e.g., heart rate) network?
• Emotion network?

• What is the function of each adrenal-related

cerebellar hotspot?
 BASIS FOR NEW HYPOTHESES
• Same procedure, different part of the body
• Lesion Studies
 FUNCTIONAL ZONES OF CEREBELLUM

• Anterior Lobe and Lobule VIII are

functionally interconnected w/
Sensorimotor Cortices
• Posterior Lobes and Lateral Lobules
VI & VII are functionally
interconnected w/ Frontal and
Parietal Association Areas

Note: Figure obtained from Stoodley, C. J., & Schmahmann, J. D. (2018). Functional topography of the human cerebellum.
Handbook of Clinical Neurology, 154, 59–70. https://doi.org/10.1016/B978-0-444-63956-1.00004-7
 OUR NEXT STEPS
• What neural network is each adrenal-related
cerebellar hotspot part of?
• Motor network- Anterior Vermis Hotspot?
• Physiologic response (e.g., heart rate) network- Posterior Vermis Hotspot?
• Emotion network- Posterior Vermis Hotspot?
ACKNOWLEDGMENTS
• Ronald R. Seese, M.D., Ph.D.
• Peter L. Strick, Ph.D.
• Priyamvada Roy Guha
• Shruthi Balasubramaniyan
• Molllie Hartup
• Carmen Panaitof, Ph.D.
• Dr. Lindsay Harsey, DO
• Kelly Wisman, PA-C
• Cathy Medlen
• Akron Children’s Hospital NeuroDevelopmental
Science Center (NDSC)
• University of Pittsburgh Systems Neuroscience
Institute (SNI)
QUESTIONS?
HOW DOES IMMUNOHISTOCHEMISTRY
WORK?

Esposito, R. (2019). What are the different detection methods for IHC? Enzo Life Science.
https://www.enzolifesciences.com
WHY NOT HUMANS?
• Current imaging technology is
inadequate
• We are unable to see the relationship
between non-adjacent neurons
• Also, limited to the Brain
• Thus, how are we able to define neural
networks, consisting of 5 and 6-neuron
chains, between the brain and organs
outside the CNS?

• Also, unethical to inject humans with

Rabies Virus!
 WHY ARE MONKEYS NEEDED
TO MAP THE CIRCUIT?
• Cerebello-cortical networks differ between rodents and
primates.
• Many brain sites that influence the adrenal medulla are
absent in rodents.

• Defining the cerebellar sites that influence autonomic output

in monkeys allows us to define the clinically relevant
anatomical sites in a model system closest to humans.
• These could be sites to examine with MRI in patients
with prominent dysautonomia
• These could be sites to target with TMS or other novel
therapies for dysautonomia

Cebus
 WHAT ABOUT THE HEMISPHERIC
LABELING?
• Based on preliminary data, I hypothesize that
these adrenal-related hemispheric areas of the
cerebellum project through the dentate nucleus
• The dentate is inter-connected with the
prefrontal cortex
• These cerebellar sites may be involved in the
cognitive and emotional control of the fight-
or-fight response
 HEMISPHERIC LABELING CONTINUED…

• Ventral Dentate connected w/

Cerebellar Crus I and Prefrontal
Cortex

Note: Figure obtained from Stoodley, C. J., & Schmahmann, J. D. (2018). Functional topography of the human cerebellum.
Handbook of Clinical Neurology, 154, 59–70. https://doi.org/10.1016/B978-0-444-63956-1.00004-7