Basal ganglia & cerebellum Flashcards
Where are the basal ganglia located?
On either side of the thalamus
How many main nuclei are the basal ganglia composed of?
4
What are the four main basal ganglia nuclei? What are these composed of?
- The striatum - composed of the caudate nucleus and the putamen
- The external and internal segments of the globus pallidus
- The subthalamic nucleus
- The substantia nigra composed of the pars compacta and the pars reticulata
What does the direct pathway do?
Facilitates motor output
What does the indirect pathway do?
Inhibits motor output
Draw the direct and indirect pathways
See essay plan
Where does most input to the basal ganglia originate from?
The frontal or parietal lobes
What is input to the basal ganglia recieved by?
Medium spiny neurones
What are the two major outputs of the basal ganglia?
Ascending - to the thalamus for form thalamocortical relay
Descending - to upper brainstem structures (such as the superior colliculus and reticular formation)
Output is exclusively to areas involving higher processing of movement - there is no output to the spinal cord
Describe the direct pathway
In this pathway, excitatory glutamatergic connections from the cortex excite the GABAergic medium spiny neurons of the striatum
Striatal output inhibits Gpi and SNr, and so reduces GPi inhibition on the thalamus
Hence stimulation of the direct pathway results in disinhibition of the thalamus, allowing the thalamus to release excitatory glutamate to stimulate enhanced activity of the motor cortex
This is disinhibition
Describe the indirect pathway
Glutamatergic cortical neurons excite striatal GABAergic neurones which decrease activity of the GABA GPe neurones
This results in disinhibition of neurons in the STN, increasing their activity
These are excitatory
His ultimately leads to increased activity of GABAergic GPi which increases inhibiton of thalamic neurones
This results in decreased motor activity
What is the hyperdirect pathway
Inhibitory connection from the cortex to the STN
Where does dopamine input go from and to?
SNc to the striatum
What does dopamine do to the direct and indirect pathways?
Activates direct
Inhibits indirect
How is it able to have these different effects on the direct and indirect pathways?
Binds to different receptors on the GABAergic neurones of the striatum
- Dopamine can bind to D1 receptors, which are Gαs-coupled and so stimulate the neurons in the direct pathway
In contrast, neurons within the striatum involved in the indirect pathway express D2 receptors, which are Gαi-coupled, and so the binding of dopamine inhibits their firing
In both instances, DA therefore facilitates movement.
How are D1 receptors able to activate neurones? What is the underlying mechanism?
Stimulate the adenylyl cyclase pathway, where ultimately, PKA is stimulated which is involed in many downstream pathways. For instance, different ion channels may be modulated, such as voltage-gate Na+ channels, Ca2+-activated K+ channels and inwardly rectifying K+ channels. Upregulation of these ultimately leads to larger MSN depolarisation in the direct pathway.
What sort of disorder is PD? Hypokinetic or hyperkinetic?
Hypokinetic
think about there being a loss of DA neurones
Characteristic features of PD
A Sexy Boy Rang To Speak Akinesia Stooped posture Bradykinesia Rigidity low frequency Tremour Shuffling gait Many patients also suffer deficits of cognition as the disease progresses
What causes PD?
Deficiency of dopamine in the BG resulting from degenerton of dopaminergic neurones in the SNc
Which nucleus has a similarity to GPi?
Pars reticulata
What is thought to be the main role of the BG?
Planning and control of complex motor behaviour by selectively activating some movements and suppressing others
Which thalamic nuclei modify signals from the basal ganglia?
Ventral anterior and ventral anterior
Describe the principle neruotransmitters involved in this system
Excitatory (glutamate) inputs from cerebral cortex to striatum, and from STN to GPi
Inhibitory (GABA) from striatum, GPi and GPe
Dopaminergic from SNc to striatum
How may loss of dopamine explain the symptoms of PD?
- Tremors arise from inability to select movement
- BG plays role in scaling of movement - PD patients have bradykinesia, shuffling gait and cramped handwriting
Describe briefly causes of PD?
Single gene mutations - e.g. in alpha synuclein gene cause accumulation of alpha synuclein in DA neurones and formation of Lewy bodies
Environmental contributions - MPTP has toxic effects that can induce PD symptoms
Describe MPTP
MPTP is a prodrug for neurotoxin MPP+
Inhibitions complex I of the ETC → cell death
(also decreased ATP → downstream increase in ATP production)
Describe the major may of treating PD
L-DOPA → dopamine precursor that crosses BBB
Administered alongside a DOPA decarboxylase inhibitor e.g. carbidopa - which cannot cross the BBB → this prevents peripheral dopamine formation, increasing the amount that reaches the CNS
Problems with L-DOPA
- Dyskinesias Effectiveness reduces as the disease progresses - as more neurones die, the uptake mechanism of DA by healthy neurones is lost and so large changes in extracellular DA occur → periods of hyperkinesia and hypokinesia - Do not prevent disease progression - postural hypotension - dysrhythmias - depression - psychosis
Aside from L-DOPA, what may used used as a treatment of PD?
Dopamine agonists
Inhibitors of dopamine uptake such as MAOβ or COMT inhibitors → increase EC DA
Is HD hyper- or hypokinetic?
Hyperkinetic
What neurones degenerate in the BG in HD? What does this lead to?
Striatal GABA medium spiny neurones of the indirect pathway
Reduces the action of the indirect pathway - bias toward direct
Characteristics of HD
ABCDEF
Ballism (undesired violent flinging of the limbs)
Chorea (fragmented, spontaneous and uncontrollable body movements)
Dystonia (slow twisting movements and abnormal posture
Also show personality changes and dementia
Describe hemiballismus
Rare movement disorder
decrease activity of STN
ballistic movement of the limbs
Occurs due to stoke, trauma etc
Draw basal ganglia anatomy
See online
Cerebellum - ipsi- or contralateral to rest of body?
Ipsilateral
Describe the function of the cerebellum
sensory-motor integration,
coordination of motor function, comparing ‘intention’ with ‘performance’
What does the cerebellum act in concert with?
The motor cortex and the basal ganglia
Where does the cerebellum sit?
Posterior cranial fossa of the skull
What separates the cerebellum and the cerebrum?
Tentorium cerebelli
What joins the two hemispheres of the cerebellum?
The vermis
What are the three lobes that the cerebellum can be divided into?
Anterior lobe
Posterior (or middle) lobe
Flocculonodular lobe
What two fissures divide the cerebellum
The primary fissure - separates the anterior and posterior lobe
The posterolateral fissure - separates the flocculonodular lobe and the posterior lobe
What are ridges of the cerebellum called?
Folia
How many lobules of the cerebellum are the?
10
Describe the cerebellum in terms of grey and white matter
Outer layer of grey matter (cortex) and an inner core of white matter surrounding deep cerebellar nuclei
What lies ventral and dorsal to the superior vermis?
The anterior and posterior cerebellar notches
What splits the left and right cerebellar hemispheres?
Falx cerebelli
What are the large rounded swellings anteriorly on either side of the inferior vermis?
Tonsils
What is an extension of the inferior vermis (between the tonsils)?
Nodule which extends downwards into the uvula
Which cerebellar fissure has no functional significance?
The horizontal fissure
What does the superior vermis extend into?
Onto the superior medullary velum, as a single lamella of cortical tissue, the lingula
List the cerebellar peduncles
Three peduncles
- the superior cerebellar peduncle
- the middle cerebellar peduncle
- the inferior cerebellar peduncle
What do the cerebellar peduncles do?
They connect the cerebellum to the brain stem
What travels through the peduncles?
Afferent and efferent cerebellar tracts going to and from the ipsilateral cerebellar cortex
What does the superior cerebellar peduncle connect the cerebellum to?
Midbrain
What does the middle cerebellar peduncle connect the cerebellum to?
The pons
What does the inferior cerebellar peduncle connect the cerebellum to?
Medulla and spinal cord
What tracts run through the inferior cerebellar peduncles?
- Afferent tracts carry ipsilateral proprioceptive information from the spinal cord
- Efferent tract composed primarily of Purkinje cell axon
What are the functional divisions of the cerebellum? What do these do?
Vestibulocerebellum (balance/posture)
Spinocerebellum (motor execution)
Cerebro-cerebellum (motor planning)
Where is the spinocerebellum?
Vermis and intermediate zones
Where is the cerebrocellum?
Lateral hemispheres
Where is the vestibulocerebellum
Flocculonodular lobe
Pneumonic to remember deep cerebellar nuclei
Dont Eat Greasy Food - Dentate Interposed nucleus made up of: - Emboliform nucleus - Globose nucleus - Fastigial
Where can the dentate nucleus be found?
Lateral hemisphere
Where can the interposed nuclei be found?
Paravermal and vermal area
Where can the fastigial nucleus be found?
Primarily associated with the flocculnodular lobe (also associated with the vermis)
What are the 3 layers of the cerebellum from top to bottom?
1 - molecular layer
2 - Purkinje layer
3 - granular layer
The DCN can be found below these
What cell types can be found in the molecular layer?
Stellate cells
Basket cells
Parallel fibres of the granule cells
What cell types can be found in the Purkinje layer?
Purkinje neurons
Draw the internal circuitry of the cerebellum
See OneNote for drawing
Describe the 5 cell types that make up the cerebellar circuitry
Purkinje – the output neurons. GABAergic, thus the output of the cerebellar cortex is inhibitory. This inhibitory P-cell outflow modulates the activity of the deep cerebellar nuclei.
Granule cells (GCs) – glutamatergic, thus excitatory
3 classes of inhibitory interneurons (GABAergic)…
- Basket – receive excitatory GC input like P-cells; axons project to neighbouring P-cells forming a basket; excitation reduces activity in adjacent ‘off-beam’ P-cells
= centre-surround antagonism
Stellate – like basket cells, -act directly on P-cells
Golgi – receive input from and project back to GCs = feedback inhibition to curtail duration of excitement of granule cells by mossy fibres
Furthermore, P-cells receive excitatory inputs from outside the cerebellum:
- One directly from the climbing fibres
- The other indirectly from the mossy fibres, via the parallel fibres of the granule cells (GCs)
Describe firing of parallel fibres
High frequency of 50-100Hz, generating a single action potential in the P cell that appears as a ‘simple spike’ (20-50Hz)
How many parallel fibre inputs from granule cells to Purkinje cells are needed to summate to cause simple spikes?
~200
Where do mossy fibres originate?
- Cerebral cortex
- Reticular formation
- Vestibular nuclei
- Spinal cord
(VARIOUS SENSORY PATHWAYS)
Were do climbing fibres originate?
- Inferior olive
How many climbing fibres does one Purkinje cell recieve input from?
1!
But makes about 300 synapses
Describe the effect that climbing fibres have of Purkinje cells?
Each AP in the climbing fibre (1-10Hz) elicits a prolonged depolarisation in the associated P cell, due to the prolonged activation of voltage-gated Ca2+ channels, resulting in a complex spike
What are the two types of electrical activity a P cell may elicit?
Simple and complex spike
Causes of cerebellar lesions
Stroke
tumour
trauma
congenital malformations
What are the 3 hallmarks of patients with cerebellar damage?
1 - postural ataxia → characterised by incoordination of axial muscles and subsequent postural instability and wide-based, staggering gait
2 - action tremors → with oscillations of 3-4Hz that worsen with directed movement due to disruption of the mechanism for detecting and correcting movement errors
3 - hypotonia → as under normal circumstances the deep cerebellar nuclei send ‘reinforcing’ signals to the motor cortex and brainstem motor nuclei, serving to increase tone, thus is the deep nuclei are lost, there is an initial slight decrease in tone (however, after a few months, the motor cortex compensates by increasing its intrinsic activity, and the hypotonia disappears
What are other signs of cerebellar lesions?
Improper measuring of distance in movements e.g. tendency to over- or under-reach
Difficulty articulating words due to lack of error correction in the movement of neck muscles required to produce speech
Difficulty performing rapid alternative movements e.g. finger-to-nose tests
NYSTAGMUS
Which motor system is the cerebellum a part of?
Extrapyramidal (does not go through the pyramids of the medulla and descend) - instead sends fibres to branches of descending fibres to modify descending input
Discuss efferent tracts from superior cerebellar peduncle
- efferent to the contralateral thalamus (cerebellothalamic tract/dentothalamic)
- also cerebellorubral (dentorubrothalamic) → to the contralateral red nucleus
- also rubrospinal (if red nucleus gets activated)
Discuss afferent tracts from the superior cerebellar peduncle
Most prominent is the ventral spinocerebellar tract
Also tectocerebellar fibres
What are the two SCPs connected by?
Anterior medullary velum
What does the medial cerebellar peduncle do?
Cortico-ponto-cerebellar afferents (which can leave via the SCP)
What does the ICP receive input from?
- Dorsal spinocerebellar tract (proprioceptive information from the lower trunk and limb)
- Cuneocerebellar tract (proprioceptive information from the upper limb and neck - from the ipsilateral asscessory cuneate nucleus)
- Vestibulocerebellar tract (from inner ear)
- olivocerebellar tract (from proprioceptors - enters as a climbing fibre)
- reticulocerebellar (all sensory)
What does output from the fastigial nucleus output control?
MEDIAL DESCENDING SYSTEMS → to proximal muslces
What does output from the interposed nuclei control?
LATERAL descending systems → more distal mouscles of fine movement control
Lesions of vestibulocerebellum
Nystagmus, head tilt, circling gate
Lesions of spinocerebellum
Impaired gait indicative of abnormal spinal control of walking
Lesions of cerebrocerebellum
Inaccuracy of reaching and clumsiness of hand movements, or impaired voluntary control of body partd
