**3. The cerebellum**

The cerebellum (Latin, *little brain*) is located in the posterior cranial fossa. Classically, the cerebellum has been linked to motor behaviors; however, more recent studies provide evidence for a role of the cerebellum in higher functions such as cognition, language, and social and affective behaviors [18].

### **3.1 Cerebellar anatomy**

Structurally, the cerebellum is constituted of ten lobules: lobules I through V (which form the anterior lobe), lobules VI through IX (posterior lobe), and lobule X (flocculonodular lobe). Lobules VII and VIII are further subdivided (VIIA and VIIB

#### *The Cerebellum and Autism: More than Motor Control DOI: http://dx.doi.org/10.5772/intechopen.85897*

and VIIIA and VIIIB); besides, the hemispheric extension of lobe VIIA is expanded and forms two major lobules, Crus I and Crus II. Dividing the cerebellum ventrally into two hemispheres, there is a central midline called the vermis (**Figure 2**) [20]. Within this anatomical division, a functional division according to the connection of each lobe can be found, establishing a topographic organization (see Subsection 3.2).

At the cellular level, the cerebellum is composed of an outer cortex constituted of gray matter, the cerebellar cortex, and an inner core formed mainly by white matter which encloses the deep cerebellar nuclei, the sole output channel of the cerebellum (see below). The cerebellar cortex is structured in three different cell layers: (1) *Molecular layer*: it is the outer layer, and it is composed of two types of cells, basket, and stellate neurons. Both are inhibitory and are part of the regulatory system of Purkinje cells. (2) *Purkinje cell layer*: it is located below the molecular layer. The Purkinje cells (PCs) represent the only output from the cerebellar cortex and are inhibitory. These neurons have a wide dendritic arbor, which extends to the top of the surface of the molecular layer, and project their axons to the deep cerebellar neurons in the inner cerebellar core, which are the only output of the cerebellum. (3) *Granular layer*: it is the deepest layer of the cerebellar cortex, and it is composed of excitatory granule cells which send their axons toward the molecular layer, forming the parallel fibers and making contacts with dendrites of PC. Granule neurons together with basket and stellate cells in the molecular layer constitute the main regulatory system of PC. Inhibitory interneurons—Golgi cells—are also found within the granular layer and act by altering the mossy fiber-granule cell synapse (see below). The Golgi cells receive input from the parallel fibers and provide an inhibitory feedback to the cells of origin of the parallel fibers (the granule cells).

Neurons in the deep cerebellar nuclei represent virtually all the output from the cerebellum. They receive inhibitory information from the PC and excitatory inputs from outside the cerebellum through the mossy and climbing fibers. The *climbing fibers are* originated in the brain stem (posterior part of the brain, continuous to the spinal cord, composed by the midbrain, the pons, and the medulla oblongata), particularly in the inferior olivary nucleus of the medulla oblongata. These axons

#### **Figure 2.**

*Structural anatomy of the human cerebellum. Representation of the cerebellar lobules: anterior, posterior, and flocculonodular and their subdivisions. Lobules VII and VIII are further subdivided into lobules A and B. Crus I/Crus II constitutes further subdivisions of lobule VIIA. The vermis represents a midline separating the cerebellum in two hemispheres. Modified from [20].*

make excitatory synapses with PC dendrites and with neurons in the deep cerebellar nuclei. The *mossy fibers* originate from several parts of the brain and spinal cord. These fibers form excitatory synapses with granule cells and with neurons of deep cerebellar nuclei. In turn, PCs receive two types of excitatory input from outside the cerebellum, one directly from the climbing fibers and the other indirectly via the parallel fibers of the granule cells (**Figure 3**) [29]. Anatomical investigations in animals and postmortem humans have established that cerebro-cerebellar connections are contralateral to each other and include an efferent cerebello-cortical pathway from the cerebellar nuclei to the cerebral cortex through the thalamus and an afferent cortico-cerebellar pathway through the pons.
