Microanatomy of the Cerebellum

Overview: The Three-Layered Cortex

The Five Cell Types of the Cerebellar Cortex

1. Purkinje Cells

• Among the largest neurons in the CNS
• Cell bodies form a single row in the Purkinje cell layer - flask-shaped, prominent, easily recognized on histology
• Dendrites extend up into the molecular layer with an elaborate, markedly flattened, fan-like arborization oriented perpendicular to the long axis of the folium
• Axons project downward through the white matter to the deep cerebellar nuclei (especially dentate) and to vestibular nuclei
• They are the sole output of the cerebellar cortex
• They are inhibitory (GABAergic) - they inhibit the deep nuclear cells
• Under resting conditions, Purkinje cells fire tonically at ~50-100 action potentials/second (Guyton & Hall)
• In rabies, Negri bodies (eosinophilic, 2-10 µm intracytoplasmic inclusions) are characteristically found in Purkinje cell cytoplasm (Histology: A Text and Atlas)

2. Granule Cells

• Located in the deep granular layer - so tightly packed they "rival the total number of cells in the remainder of the nervous system" (Neuroanatomy through Clinical Cases)
• Small neurons with round, dark-staining nuclei
• Receive excitatory input from mossy fibers
• Send axons up into the molecular layer, where each axon bifurcates into a T-shape, forming parallel fibers that run longitudinally along the folium (parallel to its long axis)
• Parallel fibers run perpendicular to the flat Purkinje dendritic trees and make excitatory synaptic contacts with numerous Purkinje cells en passant
• Granule cells are excitatory (glutamatergic)

3. Basket Cells

• Located in the molecular layer
• Inhibitory interneurons
• Stimulated by parallel fibers
• Send axons transversely (at right angles to the parallel fibers) to wrap around the cell body of Purkinje cells - forming characteristic basket-like synaptic endings around the Purkinje soma
• Produce lateral inhibition of adjacent Purkinje cells, sharpening the cerebellar signal (Guyton & Hall)

4. Stellate Cells

• Also located in the molecular layer, in its outer portion
• Inhibitory interneurons (similar function to basket cells)
• Stimulated by parallel fibers; send inhibitory axons laterally to Purkinje cell dendrites
• Cause lateral inhibition alongside basket cells

5. Golgi Cells

• Located in the granular layer near the upper border
• Receive excitatory input from parallel fibers (and mossy fibers)
• Send inhibitory axons back onto granule cell dendrites within the cerebellar glomerulus (see below)
• Act as a feedback inhibitory system on granule cells

Afferent Fiber Systems

Mossy Fibers

• Arise from multiple sources: spinal cord, pontine nuclei, vestibular nuclei, and others
• Terminate in the granular layer at specialized synaptic complexes called cerebellar glomeruli
• Make excitatory synapses onto granule cell dendrites (and deep nuclear cells)
• Input to Purkinje cells is indirect (via granule cell → parallel fiber → Purkinje dendrite)
• Produce simple spikes in Purkinje cells - short-duration, weak action potentials

Climbing Fibers

• Arise exclusively from neurons in the contralateral inferior olivary nucleus (medulla)
• Pass through white matter and "climb" along the Purkinje cell soma and proximal dendrites, forming ~300 powerful excitatory synapses per Purkinje cell
• One climbing fiber supplies only 5-10 Purkinje cells (a far more focused system than mossy fibers)
• Produce a characteristic complex spike in Purkinje cells - a prolonged (up to 1 second), powerful initial spike followed by a trail of weaker secondary spikes (Guyton & Hall)
• Also send collaterals to deep nuclear cells

The Cerebellar Glomerulus

• Central element: mossy fiber rosette (enlarged axonal terminal)
• Around it: granule cell dendrites (receive excitatory input from mossy fiber)
• Also present: Golgi cell axonal terminals (provide inhibitory input to granule cell dendrites)
• The whole complex is enclosed by a glial sheath
• These glomeruli appear as pale "islands" in the darkly-staining granular layer on histology

The Functional Unit

• Deep nuclear cells receive tonic excitatory drive from mossy and climbing fiber collaterals
• They are simultaneously under tonic inhibition from Purkinje cells
• Normally, excitation slightly predominates, maintaining moderate tonic output
• During a rapid motor movement:
  1. Deep nuclear cells are first rapidly excited (via mossy/climbing fiber collaterals)
  2. Milliseconds later, Purkinje cell feedback inhibition arrives - acting as a "delay-line negative feedback" that damps the movement and prevents overshoot

Summary Table: Cell Types at a Glance

Key Histological Points for Exams

• The three layers (molecular, Purkinje, granular) are unmistakable on H&E staining
• Purkinje cells are uniquely identifiable by their large flask-shaped soma in a single row
• The granular layer is densely basophilic due to tightly packed small nuclei
• Negri bodies in Purkinje cells = pathognomonic of rabies
• Mossy fibers create pale glomerular islands in the granular layer
• The entire output of the cerebellar cortex is inhibitory (Purkinje axons → deep nuclei)

Sources: Histology: A Text and Atlas (Pawlina), Neuroanatomy through Clinical Cases (Blumenfeld), Guyton and Hall Textbook of Medical Physiology, Ganong's Review of Medical Physiology 26th Ed