Cerebellar Histology & Circuitry Histology > Neurological System > Neurological System CEREBELLAR HISTOLOGY & CIRCUITRY SUMMARY OVERVIEW Gross Anatomy • The folding of the cerebellum into lobes, lobules, and folia allows it to assume a tightly packed, inconspicuous appearance in the posterior fossa. • The cerebellum has a vast surface area, however, and when stretched, it has a rostrocaudal expanse of roughly 120 centimeters, which allows it to hold an estimated one hundred billion granule cells — more cells than exist within the entire cerebral cortex. - It is presumed that the cerebellum's extraordinary cell count plays an important role in the remarkable rehabilitation commonly observed in cerebellar stroke. Histology Two main classes of cerebellar nuclei • Cerebellar cortical neurons • Deep cerebellar nuclei CEREBELLAR CORTICAL CELL LAYERS Internal to external: Subcortical white matter Granule layer (highly cellular) • Contains granule cells, Golgi cells, and unipolar brush cells. Purkinje layer 1 / 9 • Single layer of large Purkinje cell bodies. • Purkinje cells project a fine axon through the granule cell layer. - Purkinje cells possess a large dendritic system that arborizes (branches) extensively and a single fine axon. Molecular layer • Primarily comprises cell processes but also contains stellate and basket cells. DEEP CEREBELLAR NUCLEI From medial to lateral: Fastigial Globose Emboliform Dentate The globose and emboliform nuclei are also known as the interposed nuclei • A classic acronym for the lateral to medial organization of the deep nuclei is "Don't Eat Greasy Food," for dentate, emboliform, globose, and fastigial. NEURONS/FUNCTIONAL MODULES • Fastigial nucleus plays a role in the vestibulo- and spinocerebellum. • Interposed nuclei are part of the spinocerebellum. • Dentate nucleus is part of the pontocerebellum. CEREBELLAR CIRCUITRY Overview • Three main types of cerebellar afferent fibers exist, which innervate both the deep cerebellar nuclei and the cerebellar cortex. Climbing fibers (olivocerebellar fibers) • Originate solely from the inferior olive and pass via the contralateral inferior cerebellar peduncle to the cerebellum. • Probably use glutamate (but may use aspartate). • Each Purkinje cell is innervated by a single olivocerebellar climbing fiber. 2 / 9 Mossy fibers • Excitatory fibers derived from diffuse cell populations within the brainstem and spinal cord. • Like the climbing fibers, they use glutamate. • Note that this pathway represents the inferior arm of the triangle of Guillain-Mollaret. Multilayered fibers (aka monoaminergic fibers). • Derived from neurobehavioral centers in the brainstem and diencephalon, such as the locus coeruleus, raphe nucleus, and the tuberomammillary nucleus of the hypothalamus. • They are considered monoaminergic because their cells of origin are generally associated with a single neurotransmitter type: the locus coeruleus is noradrenergic, the raphe nucleus is serotinergic, and the tuberomammillary nucleus is histaminergic. DEEP CEREBELLAR NUCLEI OUTFLOW • Deep cerebellar nuclei send excitatory fibers to structures throughout the central nervous system. • The majority of efferent information that leaves the cerebellum does so from the deep cerebellar nuclei, which act primarily through the excitatory neurotransmitter glutamate. MODULATION OF THE DEEP CEREBELLAR NUCLEI • The molecular and granule cell layers filter and temporally pattern information as it is transmitted to the Purkinje layer. • The Purkinje layer is the sole recipient of this post-processed information and sends inhibitory fibers to the deep cerebellar nuclei via the inhibitory neurotransmitter gammaaminobutyric acid (GABA). • Thus the cerebellar cortex, acting through the Purkinje layer, is an important modulating force on the deep cerebellar nuclei. FULL TEXT OVERVIEW General Anatomy • Here, we will draw learn the histology and circuitry of the cerebellum. • Begin this diagram with a saddle-shaped cerebellar hemisphere. • Include along the surface a single fold, called a folium. - We see that the folding of the cerebellum into lobes, lobules, and folia allows it to assume a tightly packed, 3 / 9 inconspicuous appearance in the posterior fossa. - The cerebellum has a vast surface area, however, and when stretched, it has a rostrocaudal expanse of roughly 120 centimeters, which allows it to hold an estimated one hundred billion granule cells: more cells than exist within the entire cerebral cortex. - It is presumed that the cerebellum's extraordinary cell count plays an important role in the remarkable rehabilitation commonly observed in cerebellar stroke. Histology • Now, indicate that the two main classes of cerebellar nuclei are the cerebellar cortical neurons and the deep cerebellar nuclei. • Draw a magnified view of the folium in order to show the different cerebellar cortical cell layers. From internal to external, they are: • The subcortical white matter. • Granule layer. • Purkinje layer. • Molecular layer. HISTOLOGY OF THE CEREBELLAR LAYERS Now, let's look at a histological section of these layers. Molecular Layer • Show that the molecular layer primarily comprises cell processes but also contains stellate and basket cells. • The Purkinje layer contains a single layer of large Purkinje cell bodies. • The granule layer is highly cellular: it contains granule cells, Golgi cells, and unipolar brush cells. Then, label the white matter. Purkinje Layer Next, let's study the Purkinje and granule cells at higher resolution. • Indicate the cell body of a Purkinje cell. • Indicate its neighboring cell's dendritic system, which arborizes extensively within the molecular layer. • Indicate a granule cell. • Purkinje cells project a fine axon through the granule cell layer. 4 / 9 Purkinje cell Next let's draw out the major features of a Purkinje cell. • Draw a Purkinje cell. • Show its cell body. • Draw its nucleus. • Indicate the nucleolus. • Show its dendritic system. - Purkinje cells possess a large dendritic system that arborizes (branches) extensively and a single fine axon. DEEP CEREBELLAR NUCLEI Next, let's address the centrally located deep cerebellar nuclei. General Organization • From medial to lateral, they are the fastigial, globose, emboliform, and dentate nuclei. - Show that together the globose and emboliform nuclei are also known as the interposed nuclei. • A classic acronym for the lateral to medial organization of the deep nuclei is "Don't Eat Greasy Food," for dentate, emboliform, globose, and fastigial. Modules Indicate that the deep cerebellar nuclei parse into specific functional modules: • The fastigial nucleus plays a role in the vestibulo- and spinocerebellum. • The interposed nuclei are part of the spinocerebellum. • The dentate nucleus is part of the pontocerebellum. CEREBELLAR CIRCUITRY Now, let's show the flow of information through the cerebellum. • Re-draw the layers from inside to out: • White matter, granule layer, Purkinje layer, and molecular layer. • Draw the deep cerebellar nuclei. Cerebellar Afferent Fibers 5 / 9 • Indicate that there are three main types of cerebellar afferent fibers: climbing fibers, mossy fibers, and multilayered fibers (aka monoaminergic fibers). - All three fibers innervate both the deep cerebellar nuclei and the cerebellar cortex. - Now, indicate that the molecular and granule cell layers filter and temporally pattern information as it is transmitted to the Purkinje layer. Climbing Fibers (olivocerebellar tract) • Show that climbing fibers (olivocerebellar tract) are excitatory fibers that originate solely from the inferior olive and pass via the contralateral inferior cerebellar peduncle to the cerebellum. - Debate exists as to whether climbing fibers use the excitatory neurotransmitter aspartate or glutamate, but it seems most probable that they use glutamate. • Indicate that these olivocerebellar fibers are distinct in that each Purkinje cell is innervated by a single olivocerebellar climbing fiber. - Note that this pathway represents the inferior arm of the triangle of Guillain-Mollaret. Mossy Fibers • Now, show that the mossy fibers are excitatory fibers derived from diffuse cell populations within the brainstem and spinal cord. They, like the climbing fibers, mostly use the excitatory neurotransmitter glutamate. Multilayered Fibers • Lastly, show that the multilayered fibers are derived from neurobehavioral centers in the brainstem and diencephalon, such as the locus coeruleus, raphe nucleus, and the tuberomammillary nucleus of the hypothalamus. - Whereas the climbing and mossy fibers are unquestionably excitatory, the role of the multilayered fibers is less uniform. - They are considered monoaminergic because their cells of origin are generally associated with a single neurotransmitter type: the locus coeruleus is noradrenergic, the raphe nucleus is serotinergic, and the tuberomammillary nucleus is histaminergic. DEEP CEREBELLAR EXCITATORY FIBERS • Next, show that the deep cerebellar nuclei send excitatory fibers to structures throughout the central nervous system. - The majority of efferent information that leaves the cerebellum does so from the deep cerebellar nuclei, which act through the excitatory neurotransmitters glutamate, most notably. • Indicate that the Purkinje layer, which is the sole recipient of this post-processed information, sends inhibitory fibers to the deep cerebellar nuclei. • Thus the cerebellar cortex, acting through the Purkinje layer, is an important modulating force on the deep cerebellar nuclei. The Purkinje