Cerebellum and pathways

Objectives - cerebellum Identify the anatomical divisions of the cerebellum Identify the functional divisions of the cerebellum Explain what observable functions each division of the cerebellum is involved with Describe each afferent and efferent pathway – structure, function, neurotransmitters, and neuron type if applicable Describe or draw the layers of the cerebellar cortex Describe or draw the types of neurons in the cerebellar cortex Identify which neurons are excitatory (glutamate & aspartate) and which are inhibitory (GABA) Explain how the neurons in the cerebellar cortex interact

Plan of attack Lecture 9 – cerebellar structure and organization, afferent cerebellar pathways, efferent cerebellar pathways Lecture 10 –cerebellar histology

Overall function Ataxia with intention (action) tremor: https://www.youtube.com/watch?v=5eBwn22Bnio Ataxia with gross limb movement dysfunction: https://www.youtube.com/watch?v=qKGicpQLt6M Ataxic Gait: https://www.youtube.com/watch?v=FpiEprzObIU Dysmetria: https://www.youtube.com/watch?v=jnQcKAYNuyk Dysdiadochokinesia: https://www.youtube.com/watch?v=gNZFSUdL_uc Ataxia – without coordination Discuss intention vs. resting tremor Dys – bad, difficult, disordered Diadochokineasia – alternating sequential movements Metria – range of movement

Anatomical structure Gray Cortex! (Folia = sulci and gyri) Floculonodular lobe Anterior lobe Posterior lobe White Matter Cerebellar peduncles -> Arbor Vitae (tree of life!) Deep Nuclei 4 total (per hemisphere) Archi – oldest Paleo – next oldest Neo – newest

View of entire cortex Unfolded cerebellum

Functional structure Vestibulocerebellum (floculonodular lobe) Balance during stance/gait, coordinates eye and body movements Associated with vestibular nuclei Spinocerebellum (vermis and paravermis) Coordination of limb movements Associated with spinal cord directly and indirectly Cerebrocerebellum (lateral hemispheres) Planning and preparation for movement, fine motor control Associated closely with motor cortex (pre-central gyrus)

Cerebellar nuclei Lateral – Dentate Middle – Interposed; Emboliform and Globose Medial – Fastigial

Nuclei connections Fastigial – vestibulocerebellum to vestibular nuclei and eye motor centers Interposed – spinocerebellum to contralateral red nucleus Rubrospinal tract Dentate – cerebrocerebellum to thalamus Planning and control of voluntary movements All cerebellar efferents synapse in the deep nuclei

Inferior view What does the vermis do? Spinocerebellum – gross limb movements How do I know this is inferior? Tonsils are visible

Anterior view What do the nodulus and flocculus do? Vestibulocerebellum – balance in gait and stance, integration of eye movements What does the tonsil do? (posterior lobe, paravermis) spinocerebellum – gross limb movements What do the large hemispheres do? Cerebrocerebellum – smooth out voluntary movements, fine motor control

Cerebellar Afferents 4 Spinocerebellar Tracts Pontocerebellar Reticulocerebellar Raphecerebellar Hypothalamocerebellar Ceruleocerebellar Olivocerebellar

Spinocerebellar Tracts (cross-section)

Cuneocerebellar Pathway Information ascends in the cuneate tract Synapses in the Accessory cuneate nucleus (lateral to the cuneate nucleus in the medulla) Second neuron ascends ipsilaterally through ICP to cerebellar nuclei and cortex Entire pathway is IPSILATERAL Carries sensory information from UE

Posterior Spinocerebellar Pathway Ascends ipsilaterally in PSC tract Synapses in spinal cord Passes through ICP Ends in cerebellar cortex and nuclei Carries sensory information from LE

Rostral Spinocerebellar Pathway Ascends ipsilaterally Joins ASC (?) Enters cerebellum through SCP (like ASC) Carries sensory information from UE

Anterior Spinocerebellar Pathway Ascends contralaterally in ASC tract Crosses through the SCP Ends in ipsilateral cerebellar cortex and nuclei Carries sensory information from LE

Spinocerebellars Which is the red? Which is the blue? Which is the green? Which is missing and where would it be? All MOSSY FIBERS

Other cerebellar afferents Pontocerebellar Reticulocerebellar Raphecerebellar Hypothalamocerebellar Ceruleocerebellar All MOSSY FIBERS Know functions!

Olivocerebellar Pathway Information from Inferior Olivary Nucleus Crosses to the ICP Ends in the cerebellar cortex and nuclei CLIMBING FIBERS

Cerebellar afferent Drawing! Split the 4 spinocerebellars into 2 groups – draw 2 pathways per image Either by LE vs. UE, or by similar pathways (Cuneo and Post., Rostral and Ant.) Draw olivocerebellar tracts Add essential information to each drawing along the side: Where does the pathway decussate (if it does)? Which cerebellar peduncle does it go through? What information does it carry? What type of fibers is it? (mossy or climbing)

Cerebellar efferents Corticonuclear Nucleocortical Corticovestibular Other efferents

Cerebellar Corticonuclear Pathway “Fibers” VC = Vermal Cortex IC = Intermediate Cortex LC = Lateral Cortex Cerebellar Corticonuclear Pathway “Fibers” Cerebellar cortex (Purkinje cells) → cerebellar nuclei Cerebellar Nucleocortical Pathway “Fibers” Cerebellar nuclei neurons (Nuclei Cells) → cerebellar cortex White Matter = Arbor Vitae Where can you find Purkinje cells? Connections Between Parts of Cortex & Nuclei 1. Vermal Cortex → communicates with → Fastigial Nucleus 2. Intermediate Cortex → communicates with → Globose Nucleus & Emboliform Nucleus 3. Lateral Cortex→ communicates with → Dentate Nucleus (Lateral) * Functions: Both of these pathways function as an internal communication network within the cerebellum Dentate Globose Fastigial Emboliform

Cerebellar Corticovestibular Pathway Starts in: Purkinje cells within vermis, nodulus, & focculonodular lobe (Cerebellar Cortex) Through Inferior Cerebellar Peduncle Ends in: Vestibular nuclei within the brainstem Inf. Peduncle What does the vestibulocochlear cranial nerve do??? CN #8? Balance, Proprioception , Hearing, & Equilibrium Cerebellar Corticovestibular fibers allow communication between the cerebellar cortex & the brainstem Function of Cerebellar Corticovestibular Pathway = Combining the motor component of the cerebellum with the balance component of the vestibular nuclei allows for smooth & coordinated movements

Nuclear Efferents Dentate and Interposed nuclei Neurons cross in SCP Go to Thalamus, Pontine nuclei, Reticular formation, Red nucleus, Olivary bodies From thalamus up to cerebral cortex From other structures, straight down the spinal cord

Cerebellar Efferent Fibers & Motor Control 1. Cerebellorubral route connects the rubrospinal route cerebellum → red nucleus → SC 2. Cerebelloreticular route connects the reticulospinal route cerebellum → reticular formation → SC 3. Cerebellothalamic route connects the thalamocortical route Which then connects to the corticospinal route cerebellum → thalamus → cortex → SC *Cerebellar nuclei influence motor control Efferent Fibers make up Routes within the cerebellum that connect to the tracts/routes within the spinal cord Examples of Tracts listed in the book… Functions: rubrospinal = muscle tone reticulospinal = monitors levels of awareness/excitement; modulates sensory, autonomic, and motor activity corticospinal = somatomotor Which relate back to the main functions of the cerebellum The cerebellum influences other pathways Look at the RED Pathway: Red Nucleus - crosses thru decussation - stays on that side all the way down to SC

Takeaways – cerebellar efferents All efferents from cerebellar nuclei (Dentate, Interposed, Fastigial) Fastigial goes to vestibular nuclei Bilateral Dentate and interposed go to thalamus, red nucleus, pontine nuclei, olivary nuclei, and #RF All decussate in SCP All decussate again to go down spinal cord All information ends up being IPSILATERAL

Conclusion Read for Wednesday L-E ch. 11 pt. 1 We will discuss cerebellar histology Wed. and talk about how the plasticity plays a role a motor learning!

Objectives - cerebellum Identify the anatomical divisions of the cerebellum Identify the functional divisions of the cerebellum Explain what observable functions each division of the cerebellum is involved with Describe each afferent and efferent pathway – structure, function, neurotransmitters, and neuron type if applicable Describe or draw the layers of the cerebellar cortex Describe or draw the types of neurons in the cerebellar cortex Identify which neurons are excitatory (glutamate & aspartate) and which are inhibitory (GABA) Explain how the neurons in the cerebellar cortex interact

Histology! Cerebellar cortex histology, once understood, gives a really awesome and essential understanding to motor learning! 3 layers of cerebellar cortex Molecular (outer) layer Purkinje layer Granular (inner) layer

Reference: White area is air – outside the folia (a sulcus) Notice: Zoomed in! Reference: White area is air – outside the folia (a sulcus) Notice: molecular layer, purkinje cells, granular layer

Molecular layer Parallel fibers (axons of granular cells, telephone wires) Climbing Fibers (like vines on the purkinje tree) Dendrites of purkinje cells (tree like) Basket and Stellate cells

Purkinje layer Purkinje somata

Granular layer Granule somata Golgi cells

Reference: White area is air – outside the folia (a sulcus) Notice: Zoomed in! Reference: White area is air – outside the folia (a sulcus) Notice: molecular layer, purkinje cells, granular layer

Afferent fibers Information coming IN!! Climbing Fibers (vines) Mossy Fibers (stimulate granule cells)

Mossy fibers (afferent pathways) Come from all afferent pathways except olivocerebellar List them! Excite granular cells (parallel fibers, telephone wires) with high frequency, weak EPSP glutamate Bring in information constantly on what’s planned and what’s actually happening with somatic motor control Like the internet, all information is transmitted through telephone cable system Constant barrage of information from everywhere about everything

Climbing fibers (olivocerebellar) Powerful excitation to purkinje cells (vines on purkinje tree) glutamate Respond to interruptions in balance (from reflexes in spinal cord) Olivocerebellar Only fire when an immediate reaction is required! Like the CIA when something important is found on the internet! When something is thrown off and there is immediate danger, these neurons are a direct route to the purkinje cells and cause an immediate firing. Climbing fibers – when rock climbing, fast reactions could save your life!

Granule cells Granule cells (parallel fibers in molecular layer) Telephone wires All run parallel, highly structured in cortex

Granule cells Soma is in granular layer Axon ascends to molecular layer, splits, and runs as parallel fiber Excitatory but weak to purkinje cells – requires multiple action potentials to break threshold glutamate

Purkinje neurons Named after one of the first neuroscientists Main efferent neurons (cortex to deep cerebellar nuclei) Have a huge dendritic tree in the molecular layer Are acted on by: Parallel fibers Climbing fibers Inhibitory - GABA

Efferent fibers Purkinje neurons (inhibitory) Giant dendritic tree GABA Giant dendritic tree Weak but frequent stimulation from granule cells Which pathways? Strong but infrequent stimulation from climbing fibers Inhibit deep nuclei (DEGF)

Inhibitory interneurons Basket cells Inhibit purkinje cells Golgi cells Inhibit granule cells All GABA

Basket cells Axon terminals wrap around purkinje cell bodies like baskets Inhibit purkinje cells GABA Excited by parallel fibers Inhibit an inhibitory neuron…. Action potential allowed to propogate

Golgi cells Inhibit granule cells Located in granular layer GABA Located in granular layer Excited by parallel fibers Inhibit a neuron that excites an inhibitory neuron… action potential is allowed to propogate

Task In your team, create a short video (with phones or other devices) explaining how information enters the cerebellum, how the neurons interact, and how the information is sent out of the cerebellum. Include: Mossy fibers and pathways that fall into this category Climbing fibers and pathway(s) that fall into this category Granule cells with parallel fibers Purkinje cells Corticonuclear and nucleocortical tracts Excitation vs inhibition (and neurotransmitters) Today in class: create a plan, write up a script Post a link to your video on the wiki by Friday midnight. (part of participation grade – out of 10 points)

Figure 1. This drawing represents the cytoarchitecture of the cerebellum. Its cellular components are: 1. Basket cells. 2. Climbing fibers. 3. Purkinje neurons. 4. Golgi cells. 5. Mossy fibers. 6. Stellate cells. 7. Parallel fibers. 8. Granule cells. 9. Lugaro cells. 10. Brush cells. Also, it shows the three different layers of cerebellar cortex: molecular layer (ML), Purkinje layer (PL) and granule layer (GL), as well as the white matter (WM). Arrows points out the ascending directions of the climbing (left) and mossy fibers (right) coming from the inferior olive and the brain, respectively.

Reciprocal Inhibition Interneurons inhibit purkinje and granule cells Only excitation comes from mossy and climbing fibers Result is inhibitory outputs

Motor learning and the cerebellum Theory: When climbing fiber input and parallel fiber input occur at the same time on the purkinje cell, the post-synaptic purkinje dendrite experiences long-term depression (LTD) Beyond this is yet unknown but studying the cerebellar cortex has surfaced these three hypotheses: Learning and memory can result from modifications of synaptic transmission. Synaptic modifications can be triggered by the conversion of neural activity into intracellular second messengers. Memories can result from alterations in existing synaptic proteins. For more information, see pages 772-776 of Bear.

Cerebellum Overview Functional structure Pathways Cerebellar histology Vestibulocerebellum Spinocerebellum Cerebrocerebellum Pathways Afferents Efferents Cerebellar histology Neuron types

Organization of the Course Spinal Cord Brainstem/ Cerebellum Sensory Pathways Cerebrum Motor Pathways Cranial Nerves Other Pieces of the puzzle Overview and Development

Conclusion Start discussing the rest of the sensory pathways Monday! Assignment #2 due Monday Only 3 lectures left until Midterm Exam!! Finish creating video, post to wiki by Friday midnight!