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UCSD Summer research conference oral presentation 2013

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Chris Hissom

on 25 February 2016

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Transcript of UCSD Summer research conference oral presentation 2013

The Motor Cortex
Motor command
Originates in higher brain areas
Communicate with Primary motor cortex ( M1)
Execute- Corticospinal tract
Learn and Adjust -Subcortical loops
Return- Thalamocortical tract
Corticospinal Tract
Output to spinal cord
Regulate skeletal motor movement
Motor Cortex -> Spinal Cord (IZ or D/V Horn) -> Spinal Motor Neurons
Thalamocortical Trac
Receives input from basal ganglia
outputs onto pyramidal cells in M1

How many people...
What is plasticity?
Motor Learning
What is motor Learning?
Motor Cortex an ideal model to study plasticity

"Investigating the functional significance of corticospinal and thalamocortical neurons in learning and performance of complex behavioral tasks in the adult mammalian motor system"

Investigating the functional significance of corticospinal and thalamocortical neurons in learning and performance of complex behavioral tasks
Background Studies

Direct CST pathway contributes to fine motor control and precison grip (Lawrence et al. 1968)
Indirect CST pathways are also able to mediate discrete forelimb control in primates and is especially prevalent in lesser mammals (Isa et al. 2007)
Tracers injected into the distal forelimb musculature, of rats retrogradely label neurons in the C8 region of the spinal cord (McKenna et. al 2000)
Previous studies in our lab have been able to demonstrate structural plasticity is specific to populations of C8 neurons preferentially activated during distal forelimb reaching. (Wang et. al)

Background Studies
Research suggests that the VA/VL thalamic nuclei relay information from Basal Ganglia and Cerebellum to pyramidal cells in M1 .

Basal ganglia and cerebellum take part in motor control, motivation, gain control, coordination, and motor learning .

M1 receives input from from the ventrolateral thalamus ( Hoover and Strick 1990)
Cerebello-thalamo-cortical projections play an important role in motor control. ( Kaneko et al 2009)
VL relays motor information and motor control information from the cerebellum and the basal ganglia to motor cortex (Tlamsa and Brumberg 2010).
There are mono synaptic connections between thalamocortical afferent to the Corticospinal neurons . (Amassian and Weiner 1966)

How is our project different ?
Difference in methods
Other studies rely on lesions
Function of brain area vs function of connections
Target specific ablations
Novel method for selective ablations.
Directly target specific connection
Hypothesize and observe the functional significance of a connection during learning and performance of a complex motor task
Thalamocortical ablation
Corticospinal Ablation
Inject rats with Neuret-IL-2Rα–GFP
Forelimb Reach Training
Immunotoxin Injection
Behavioral Analysis
Dramatic decline in accuracy of distal forelimb reaching task
Repeated tendency to extend forelimb without being able to align forelimb and paw in correct position for ideal pellet retrieval
Consistent extension of forelimb drastically to the side of the apparatus instead of centered at the pellet
Display some impairments in dexterity and often drop a pellet when grasped
Display the ability to recover and improve on accuracy following CST lesions
Forelimb reaching task
Hind leg crossing
Inability to initiate motor movement
Stiff arms as rat eats
Open field analysis
Petri dish chewing
Uncoordinated turning
Torso twist
Can moderately use forelimbs for over-learned behavior such as grooming.

Future projects / Whats next
Observe and hypothesize function of different connections and their role in behavior and learning.
Two potential approaches:
Ablate the connection prior to motor learning
Ablate the connection following motor learning
isolate and ablate neurons in the thalamocortical connection used during forelimb reaching task
observe behavioral irregularities
Expected results
Behavioral disturbances that resemble Parkinson's disease
Inability to coordinate task properly
unable to adapt if task is altered
reach without direction
change in motor gain
Question: To what extent do CST neurons in the motor cortex play a role in the performance of fine motor movements?
Is the circuitry capable of plastic adaptations to compensate if a selection of the circuit is removed?
What role do CST neurons specifically play in distal forelimb motor movements?
To specifically target and ablate CST neurons without compromising surrounding circuitry
To observe behavioral effects of removing the CST circuitry and dtermine whether learning is still possible.
Expected results:
Loss of fine motor control and compromised performance
Some potential for compensation due to plasticity of CST

Dr. Jim Conner
Dr. Mark Tuszynski
Kirsten Kung
MARC Program

Evidence of Concept
What we discussed
Corticospinal conclusion and future studies
Thalamocortical conclusion and future studies
Full transcript