week 8 basal ganglia + parkinsons Flashcards
what is the Basal Ganglia? What does is control
an interconnected group of nuclei in the brain that controls voluntary movements and play a role in a variety of other behaviors, such as…
- Motor control
- Non-motor behaviors
- learning and habits
- rewards and addiction
How does the basal ganglia regulate motor control?
The basal ganglia acts as a gatekeeper for movements, selecting which actions to allow and which to inhibit. It filters out unnecessary or incorrect signals from the brain, allowing you to activate specific motor programs without using nearby muscles.
How does the basal ganglia regulate non- motor behaviors?
The basal ganglia are involved in a wide range of non-motor behaviors, including emotions, language, decision making, procedural learning, and working memory
How does the basal ganglia regulate learning and habits?
The basal ganglia play a role in learning and forming habits. The striatum, a major input station of the basal ganglia, is involved in instrumental behavior, which is learned behavior that is modified by its consequences.
How does the basal ganglia regulate reward and addiction?
The basal ganglia are involved in reward and aversion emotional stimulation
what are the symptoms of parkinsons disease
- Tremor
- Stiffness
- Bradykinesia + Hypokinesia
- Postural Instability
- Dysarthria
what are the therapies for parkinsons disease
- Levadopa (L-Dopa or edible dopamine) 1st choice but eventually causes side effects
- Dopamine agonists - being investigated as a way to avoid side effects
- Deep Brain Stimulation - used once drugs are no longer effective (SPECIFICALLY SUBTHALAMIC NUCLEUS)
- Physical Therapy
Much of what is known about the basal ganglia comes from the study of __________ _________
Parkinson’s disease
Why is data about the basal ganglia from parkinsons disease misleading?
This may be misleading because data comes from studies of a malfunctioning system, making it hard to know for sure how the system works normally.
Basal ganglia include:
- Striatum (caudate and putamen)
- Globus pallidus (internal and external)
- Substantia nigra & ventral tegmental area
(VTA) - Subthalamic nucleus
what are the inputs and outputs of the basal ganglia?
- Inputs come from Cortex
- Outputs go through Thalamus back to cortex
- This creates a feedback LOOP.
The ________ _______ are central elements of motor control circuits that are distinguished by there dependence on dopamine.
Basal Ganglia
These are three frontal sections (left half) from forebrain showing different parts of BG.
Striatum is composed of dorsal and ventral parts. The dorsal part is sometimes divided into __________ (inputs from prefrontal cortex) and __________ (inputs from motor cortex)
Caudate and Putamen
____________ ___________ is part of the dopamine synthesis pathway and is found throughout the BG.
Tyrosine Hydroxylase
Immunohistochemical labeling of ________ _________ allows clear identification of the brain areas comprising BG.
tyrosine hydroxylase
Tyrosine hydroxylase antibody: labels both ___________ and ____________ producing neurons
dopamine (DA) and norepinephrine (NE)
Example of Basal ganglia from bat brain: similar to rodent and other mammals.
Main inputs to striatum come from _______. These are __________ ___________ inputs
CORTEX ; excitatory glutamatergic
Anatomical organization of the inputs to the basal ganglia
from all parts of cortex to caudate and putamen then to SNpc
The motor cortex mainly sends commands to
brainstem and spinal cord, but also
simultaneously sends a ___________(_______) of
those commands to the BG.
copy (collaterals)
The other main input to striatum is the dopaminergic projections from _________ _______
substantia nigra (SNpc)
SN has two parts:
- Pars compacta (produces dopamine)
- Pars reticulata (Inhibitory outputs to
midbrain).
The main cell type comprising the striatum is the
Medium Spiny Neuron (MSN)
what do Medium Spiny Neuron (MSN) do?
- receive cortical excitatory inputs and dopamine inputs. MSNs send inhibitory output projections to the Globus Pallidus and SNr
- caudate MSNs send to internal GP and SNr (D-1)
- putamen MSNs send to mostly external and some internal GP (D-2)
Neurons in Globus pallidus and thalamus have _____ ________ _______ ______
high spontaneous firing rates
Excitation in neostriatum leads to…
suppression in Globus Pallidus and disinhibition of thalamus…. causing excitation of cortex.
Signal from cortex activates ___ _______ that creates an excitatory feedback to another part of cortex. This loop creates …
a loop ; temporal sequences that underlie learned motor behaviors.
Dopamine is a…
reward signal that facilitates excitatory synapses in the striatum to reinforce sequences that produce desired outcomes (with practice).
Functional Circuits of the Basal Ganglia: the motor feedback loop & learned patterns
Blue= GABAergic
Red = Glutamatergic
Functional organization of the intrinsic circuitry and outputs of the basal ganglia
Anatomical organization of the outputs to the basal ganglia
This figure illustrates how excitation from cortex can act via disinhibition of thalamus to excite cortex.
striatum activated = inhibits globus pallidus = allows thalamus to fire = excites upper motor neuron
Key is to remember that GP neurons have _____ __________ ________, so normally ________ __ __________
high spontaneous activity ; thalamus is suppressed
how is “action selection” achieved?
by releasing the preferred action from inhibition
Parkinson’s disease is characterized by:
inability to initiate movements: Striatum cannot inhibit Globus Pallidus due to lack of dopamine
Huntington’s disease is characterized by:
uncontrolled movements: arises from uncontrollable disinhibition of loop.
Two outputs from BG:
- Thalamus to cortex (corticospinal)
- SNr to midbrain (corticobulbar)
(BG has two outputs that correspond to the two motor systems)
The SN pars reticula:
- NOT the dopamine producing region
- separate BG output pathways to the midbrain
- under normal conditions SNr neurons have HIGH spontaneous rate and constantly suppress motor outputs
- selective disinhibition of SRn activates specific motor pathways
what are the two kinds of pathways through the BG?
- Direct pathway (the gas pedal) leads to excitation of cortex. uses D-1 type dopamine receptors
- Indirect pathway (the breaks) suppresses cortex (prevents unwanted movements). uses D-2 type dopamine receptors
It is hypothesized that direct and indirect pathways ensure…
- activation of correct movements while suppressing similar unwanted movements.
- Sharpens motor action selection!
Direct pathway
- main feedback loop promoting action sequences.
- Facilitated by excitatory D1-type dopamine receptors in Caudate/Putamen.
Indirect pathway is negative feedback loop through
subthalamic nucleus that suppresses action
- Acts through inhibitory D2-type dopamine receptors in Caudate/Putamen.
Assuming that motor actions are anatomically grouped by similarity, the direct and indirect pathways may…
sharpen or fine-tune which motor sequences are activated. They must be balanced.
(Parkinson’s disease and Huntington’s disease reflect an imbalance towards one or the other, producing hypo- or hyperkinetic movement disorders.)
Dopamine post synaptic excitation and inhibition
Post-synaptic excitation: (D-1)
- increased cAMP/PKA
- increased Ca2+
- alters gene expression
Post-synaptic inhibition: (D-2)
- decreased cAMP/PKA
- decreased Ca2+
- alters gene expression
Roughly ____ of medium spiny neurons (MSNs) express both D1 and D2 receptors, while the rest express one type.
40%
D1-MSNs mediate ________ and _______, while D2-MSNs mediate _________
reinforcement and reward ; aversion
Degeneration of dopaminergic neurons reduces voluntary movement in Parkinson’s disease
D-1 and D-2 receptors damaged -> neostriatum to GPe (indirect) decreases and to GPi (direct) increases -> subthalamic nucleus to GPi increases -> GPi to VA/VL of thalamus increased -> decrease excitation from VA/VL of thalamus to frontal cortex
Degeneration of medium spiny neurons increases involuntary movement in Huntington’s disease
MSNs going from GPe degenerated, GPe inhibition increase to subthalamic nucleus and GPi, subthalamic to GPi decreases, GPi to VA/VL of thalamus decreased = frontal cortex more activated
A ______ _______ produces involuntary movements resembling hyperkinesia
GABA agonist
Example of uncontrollable eye movements resulting from injection of a GABA agonist (Muscimol) into SNr.
This mimics the symptoms of Huntington’s by disrupting the balance between direct and indirect pathways through BG.
what is deep brain stimulation also used to treat?
- Tremor and dystonia (other movement disorders)
- Depression
- OCD
- Tourette syndrome
- Schizophrenia
- Epilepsy
precisely how and why DBS works is ___________
UNCLEAR
