Cerebellum/Basal Ganglia/Motor Cortices Flashcards
three main functions of cerebellum
- monitor and adjust ongoing motor behavior (precision and smoothness is poor without the cerebellum)
- contribute to motor learning
- participate in cognitive functions
four types of experiments to ID cerebellum function
- lesions give problems with coordination and balance, problems with learning new motor skills, and problems with some “higher functions”
- tract-tracing
- neural recording. Cerebellar neurons change firing frequency when limb is moved or you touch the skin
- fMRI, PET
three parts of cerebellar cortex
cerebrocerebellum
spinocerebellum (the part receive sensory inputs, somatotopic mapping)
vestibulocerebellum
three deep cerebellar nuclei
dentate nuclei
interposed nuclei
fastigial nuclei
three cerebellar peduncles
superior
middle
inferior
cerebellum talks to CNS through peduncles;
the lateral part of the cerebellar cortex communicate with dentate, the largest nuclei, and run in the middle pedunculi which receives axons from, and distribute axons to the cerebral cortex
define: vermis, additional name?
midline of cerebellum
spinocerebellum
define: flocculus, additional name?
bottom part of cerebellum
vestibulocerebellum (balance)
define: Foli, additional name?
folds of cerebellum
cerebrocerebellum
what are the inputs to the cerebellum?
- cortical input (frontal + parietal cortex -> pontine nuclei)
- vestibular nuclei
- cuneate nucleus (spinal cord, medial lemniscal pathway)
- non-sensory input: climbing fibers, exclusively arising from inferior olive
what are the outputs of the cerebellum?
via (large) deep cerebellar nuclei to cerebral cortex (via thalamus), spinal cord (through reticular formation), and center for eye control
one exception is fibers from flocculus go out of the cerebellum without contacting the deep cerebellar nuclei
input from cerebral cortex goes to_in cerebellum
input from pons goes to_ in cerebellum
input from vestibular organs goes to_ in cerebellum
input from spinal cord goes to_in cerebellum
(not in the lecture)
cerebrocerebellum
cerebrocerebellum and spinocerebellum
vestibulocerebellum
spinocerebellum, vermis
cerebrocerebellum outputs to_
spinocerebellum projects to_
vermis projects to_
(not in the lecture)
dentate nucleus-> thalamus
interposed nucleus
fastigial nucleus -> reticular formation
what are the 3 layers of cerebellar cortex?
molecular, purkinje, granular
together they form gray matter, white matter is myelinated axons
purkinje cell (output)
- inhibitory cell in cerebellum that inhibits deep cerebellar nuclear cell
- only purkinje cell project out from the cerebellar cortex to the deep cerebellar nuclei
- the dendritic tree of Purkinje cells lie in one place, perpendicular to the parallel fibers
climbing fiber (input)
- excitatory cell in cerebellum that originates in inferior olive
- STRONGly excites multiple purkinje cell, each PC receives only one climbing fiber
- all from inferior olivary nucleus, connect exclusively to Purkinje cells
mossy fiber (input)
- originates from many different sources. several mossy fibers synapse to a single granule cell
- excitatory
granule cell
- neuron within cerebellum. Receives excitatory input from mossy fibers. Bifurcates into parallel fiber
- a parallel fiber can synapse only on a specific purkinje cell, but one purkinje cell to five fibers
- forms weak excitatory synapse onto purkinje cell, thus many granule celle are needed to fire a Purkinje cell
- the only excitatory type in cerebellar cortex, converging on purkinje cell
- thre are no excitatory synapses onto other excitatory cells, preventing information and excitation from spreading
basket cell
inhibits purkinje cell in cerebellum, may regulate precise time output
where do the inputs to the basal ganglia come from?
- limb cortex
- motor cortex
- associative cortex
what are the outputs of the basal ganglia and what are their functions?
- superior colliculus: head and eye mvt
- thalamus: motor control
- pedunculo-pontine nucleus: spinal cord processing + locomotion
striatum
inputs, kinds of cells in it. DIfference between primates and rodent?
- dorsal: caudate nucleus and putamen
ventral: accumbens - glutamatergic input from all areas of cortex + thalamus
- dopaminergic input from substantia nigra compacta
- intrinsic connections: gabaergic and cholingergic
- medium sized spiny neurons and striatal interneurons
In rodents, caudate and putamen are a single structure. In primates, they are separated by internal capsule.
striatal projection cells: MSNs
- 90% of cells in striatum
- GABAergic (inhibitory)
- main output of striatum
- slow activity at rest but active during movement/learning
- MSNs considered “phasically active neurons”
striatal interneurons
- 10% of cells in striatum
- cholinergic: tonically active neurons in primates
- GABAergic
what kind of terminals are highly expressed in striatum?
dopamine (DOPA terminals)
spines of spiny neuron are the main sites of functional interactions between glut and dopaminergic inputs to the striatum
what are the three differences between the direct and indirect pathway?
indirect:
uses enkephalins
expresses D2 receptors
MSN project to GPe -> STN -> GPi/SNr
direct:
use substance P and dynorphins
express D1 receptors
MSN projects to GPi/SNr directly
GPe
Name inputs, outputs and comparative anatomy
characteristic of GPe cells
- inputs: STN (glut), striatum (GABAergic), intrinsic (local) collaterals (GABAergic)
- outputs: STN (GABAergic), GPi/SNr
- called globus pallidus in rodents
1.highly GABAergic
2. glut inputs are less abundant and distal
3. despite the abundant GABAergic innervation, GPe neurons present tonic high freq discharge
(due to GPe neuron intrinsic activity & lots of the GABA innervations are silent)
sub-thalamic nucleus (STN)
overall, inputs, outputs
- mostly glutamatergic (the only excitatory neurons in basal ganglia). Strongly excited by cortex. Lots of spontaneous activity
- inputs: glutamatergic: cortex and thalamus GABAergic: GPe
- outputs: GPe (+), GPi/SNr (+)
- reciprocal connection with GPe and STN - pacemaker activity
GPi/SNr (inner part)
inputs, outputs, how does it fire? what is it called in rodents? function?
- inputs: STN(glut), striatum + GPe (GABA)
- outputs: thalamus, brainstem
- fires at high freq
- in rodents it is called entopeduncular nucleus (EPN)
- function: have GABAergic projections to thalamus. Strong inhibition of thalamo-cortical cells
SNc (outer part)
inputs, outputs, function
- inputs: STN(+), PPN (+), striatum(-), SNr(-)
- outputs: striatum (excites D1/direct, inhibits D2/indirect), STN, GPe/GPi/SNr
- function: predict reward. i.e. fire when reward occurs and after conditioning fire when they think reward will occur. If no reward occurs, their firing is depressed
- SNc dopaminergic neuron
slow spontaneous activity;
phase activation in response to reward;
after conditioning, response to the presentation of the reward-signaling stimulus
how does direct pathway of basal ganglia facilitate movement?
cortex excites D1 in striatum > D1 inhibits GPi/SNr > GPi/SNr weaken inhibition of thalamus > motor activity strengthened
what is the function of dopamine (from SNc) in both pathway?
facilitate movement. Inhibits indirect pathway D2 and facilitate direct pathway (D1)
what are the possible functions of the basal ganglia?
- response-based inhibition (when ongoing mvt must be inhibited in response to external stimulus)
- selecting actions and suppression of potentially competing actions (‘focusing’)
- control of mvt parameters (amplitude + speed)
- motor learning
dopamine reinforces corticostriatal synapses that facilitate behavior linked to reward;
role in the acquisition and execution of motor sequences and habits
check slides for experiments related to role 2 ~ 4
how does indirect pathway of BG inhibit movement?
cortex excites D2 in striatum > D2 inhibit GPe > GPe decreases inhibition of STN > STN excites GPi/SNr > GPi/SNr strongly inhibits thalamus > motor activity weakened
difference between reflex and voluntary movements
- not stereotyped: can use different strategies to do the same task
- improves with learning
- external stimuli not necessary to evoke voluntary movement
what three processes lead to voluntary movement?
- target identification (posterior parietal): use visual inputs to identify and locate targets
- plan of action (premotor area): determine which body parts are needed for movement and in what direction they are to move
- execution of action (primary motor): commands sent to specific body parts - both direct and indirect projections to motor neurons
what is Brodmann’s area of primary and supplementary motor cortices?
4 (primary)
6 (supplementary)
projections from M1 to spinal cord and brainstem
- cortex directly project to spinal cord: pyramidal tract neurons (upper motor neuron) of the primary motor cortex make mono-synaptic connections with the lower motor neurons in the spinal cord
- cortico-motoneurons activate complex muscle patterns through divergent connections with spinal motor neurons that innervate different arm muscles
what are the functions of the primary motor cortex?
- controlling distal muscles, fine digit movement
- control conditioned and skilled movement
- functions in producing skilled and accurate movements rather than automatic/rhythmic movement
what properties do MI neurons code for?
Force. pyramidal tract neuron (PTN) activity increase as the applied force (not displacement) increases
Also direction. Cells show preference for movement in specific directions. Single neurons in M1 fire briskly in a preferred direction, but are rather broadly tuned. Overall direction can be represented by the vectored sum of the individual preferred directions of single cells
where does primary motor cortex get its input from?
- supplementary motor area
- pre-motor
- S1
where do premotor areas get their inputs from?
- posterior parietal cortex
2. prefrontal cortex
how to neurons in motor cortex get sensory feedback?
- cortico-cortical fibers from somatosensory cortex to M1
2. and by pathways from the periphery through the thalamus
describe function of premotor cortical areas, including PMd
- receive inputs from posterior parietal cortex (ventral stream, planning action)
- project to primary motor cortex
- premotor areas active before executing voluntary movement (i.e. spontaneous voluntary movements are preceded by activity in all of the premotor areas)
4.premotor neurons active in precision, not power task - canonical neurons respond to the sight of objects. Cells activity signifies how to interact with the object. (exp: different shapes of objects)
- PMd:
plays a major role in movement planning and/or preparation
6.1 selection of tasks among alternative actions
6.2 neurons with effector (left-right arm) independent tuning properties could support selection of action
the role of parietofrontal networks in reaching and grasping
Parietofrontal networks mediate the visuomotor transformation necessary for reaching and grasping
- the superior parietal cortex uses sensory information to guide arm movements toward objects in peripheral space
- the inferior parietal cortex and ventral premotor cortex contain representations of peripersonal space
what is the function of posterior parietal lobe?
not in the lecture
- supplies information for movement towards target
- information is conveyed to it from many sensor
- encodes kinematic information only (direction only)
- parietal lobe is activated move when the task is complex
(cerebellum) simple spike vs complex spike
simple when activated from parallel fibers, complex when activated from climbing fibers;
complex spikes give considerably more Ca2+ influx than simple spikes, which initiates a cascade of biochemical events
(cerebellum) cerebellar motor learning
long-lasting depression of parallel fiber synapse when Purkinje cells are activated by climbing fiber at the same time. Thereby, the output from cerebellar cortex to a sensory input signal can be modified by the climbing fiber (“a teacher”). In other words, synchronized firing of parallel fiber and climbing fiber changes the efficacy of the climbing fibers.
(cerebellum) what is the code?
hypothesis: time synchrony (not explained in details)
(cerebellum) example exam questions
- Some humans loose cerebellar function due to environmental factors, alcohol being the most common. What kind of daily-life activities would become problematic for these patients?
- What kind of animals have a cerebellum, and what is the differences and similarities between human cerebellum compared to cerebellum in other animals?
- The cerebellar cortex consists of many neuronal types, out of which two are considered more important than the others. Describe these two neuronal types, their axonal trajectories and the synapse between the two.
- Flocculus, vermis and the hemispheres are three areas of cerebellar cortex. There are three other names being used that reflect the function of approximately the same areas. Give those names and describe from which parts of the CNS they receive afferent information.
(BG) cortoco-basal ganglia-thalamocortical circuits
- motor
- oculomotor
- executive/associative
- emotion/motivation
areas of cortex project in a highly somatotopic manner to the striatum
check the slides
(BG) cortico-striatal projections
- glut inputs
- corticostriatal terminals contact dendritic spines
- each cortical neuron makes very few contacts with individual striatal neurons
- cortical terminals also contact GABAergic interneurons
(BG) thalamo-striatal projections
- glut inputs
- originate mostly in intralaminar nuclei
- thalamic afferents contact: MSNs and interneurons
(BG) cortico-subthalamic afferents
- glut inputs
- topographically and somatopically organized
- cortical terminal contact distal dendrites
- called “hyperdirect” pathway: power excitatory effects from cortex and very fast
- shorter conduction time than corticostriatal pathway
(motor cortex) What happens in the cortex after an infarct to the digit representation and subsequent rehab?
Plasticity in the cortex. Activity dependent reorganization of motor areas. Infarct zone remains unresponsive but other representations (digit, wrist, proximal) expand
(motor cortex) role of supplementary motor complex (SMA)
initiating movement
(motor cortex) readiness potential
movement of finger is preceded by the readiness potential
check the slides
