200-147 million years ago


During the evolution of the synapsid reptiles and the early mammals (a period of more than 150 million years), a number of changes evolved in the nervous system. The spinal cord became larger and its tracts were modified. The brain enlarged and included modified tracts, a more complex diencephalon, new regions of the cerebellum, and the pons. Although the organization of the mammalian cerebrum is very different from that of reptiles, it represents a reorganization and enlargement of common ancestral areas. Some regions of the cerebral cortex are shared between all mammals. Olfactory receptors were amplified and accessory structures around the eye evolved.


The overall size of the spinal cord is increased in mammals although the spinal cord doesn't extend the length of vertebral column. A number of modifications of the cranial nerves and their nuclei occur in mammals. The glossopharyngeal portion of fasciculus solitarius is reduced in mammals, some of the visceral sensory fibers from the vagus and glossopharyngeal nerves travel ventrally to the vagal dorsal efferent nucleus, the trigeminal nucleus increases in size, more occulomotor fibers cross to the opposite side of the brain, the glossopharyngeal nucleus forms part of the nucleus ambiguous, the facial nerve expands its area of innervation, and the trigeminal innervates the skin of face, lateral head, and tongue.

In the mammalian spinal cord, the dorsal horns are divided into the zona marginalis, substanctia gelatinosa of Rolando, and a main mass. Mammals possess proprioceptive collaterals to the dorsal column and from there to the nucleus gracilis and cuneatus. More of these connections are present in higher mammals. Mammals increase the size of the dorsal column and placental mammals increase the size of the nuclei cuneatus and gracilis. The mammalian spinothalamic tracts are homologous to the spino-mesencephalic and spinobulbar tracts of more primitive tetrapods. In mammals the red nucleus is larger, as is the rubrospinal tract.
In mammals, part of the lateral lemniscus proceeds to the medial geniculate nucleus of thalamus and from there to the auditory cortex. Mammals possess an external cuneate nucleus, a nucleus medialis, and a nucleus of von Monkow. The nucleus of Bechterew extends farther caudally than in reptiles.
Mammals possess separate cervical, brachial, lumbar, and sacral plexuses. It appears that a cranial shift in the expression of some Hox A genes is responsible for a forward migration of the brachial plexus of birds compared to mammals.

In mammals, the considerable expansion of the cerebrum and cerebellum also led to an expansion of the fiber tracts which travel from the body to the cerebellum, from the cerebellum to the cerebrum, and from the cerebrum to the cerebellum. At the base of the cerebellum in mammals, there is an expansion of the brainstem where all of these fiber tracts are organized. This expansion is known as the pons, which only mammals possess.
There are a number of cerebellar changes which mammals share. The cerebellar hemispheres are greatly expanded in mammals and include a central vermis. Mammals (including monotremes) develop an enlarged floccular region; a distinct parafloccular region; anterior, middle, and posterior lobes of the cerebellum; and the fissuras postpyramidalis, prepyramidalis, and uvulo-nodularis. Mammals also share the features of three cerebellar peduncles, cortico-ponto-cerebellar tracts, and three deep cerebellar nuclei: the medial (fastigial) nucleus, lateral (dentate) nucleus, and the nucleus emboliformis. The older regions of the cerebellum (the vermis, fastigal nucleus, archicerebllum) seem to have functions which are distinct from those of the neocerebellum.
In mammals, the primitive optic tectum forms the superior colliculi and the primitive tori semicirculares form the inferior colliculi. The inferior colliculus is exposed on the surface of the midbrain rather than being deep to the optic tectum and a fissure splits superior and inferior colliculi. Only mammals possess cerebral peduncles. There are increased connections between the superior colliculus and diencephalon, an increase in the medial longitudinal fasciculus, the red nucleus is more prominent, and a pedunculo-tegmental system exists.
In mammals, the diencephalon is more complex than in reptiles. The mammalian diencephalon shares a common set of nuclei which include a dorsal lateral geniculate nucleus, ventral nuclear group, anterior nuclear group, medial nuclear group, intralaminar nuclear group, lateral posterior-pulvinar complex, medial geniculate body, limitans/suprageniculate complex, and lateral part of posterior nuclear group. Many nuclei exist in the diencephalon of non-mammals, especially birds and reptiles and many of these nuclei are homologous to those found in mammals to some degree. In mammals, the medial geniculate nucleus of thalamus relays auditory information to auditory cortex, the lateral geniculate nucleus of thalamus relays visual information to visual cortex, the lateral thalamus relays information to cerebral cortex, the accessory optic nucleus is connected to the oculomotor complex rather than the cerebellum, and lemnothalamic nuclei are more developed and move caudally. Mammals possess anterior and posterior paraventricular nuclei, medial and lateral habenular nuclei, and accessory optic nuclei. The mammalian tectum is less important in visual processing and many visual fibers proceed to the thalamus. In mammals, all dorsal thalamic nuclei participate in relays to the cerebrum. The hypothalamus performs roles in heartbeat, respiration, blood pressure, and sleep.

All amniotes seem to have similar cerebral circuitry. The organization of the mammalian cerebral cortex is similar to that of the dorsal ventricular ridge in reptiles and birds. The anterior dorsal ventricular ridge is a singular structure which seems contain the cells that, after migrations which occur during the development of the mammalian brain, are homologous to the basolateral amygdala complex, the lateral neocortex, and the claustrum-endopiriform nucleus. In monotremes the first two structures, but not the claustrum-endopiriform nucleus, are present. In mammals, the formation of these regions requires the Pax-6 gene and these regions in Pax-6 mutant mice are very similar to those observed in reptiles and birds.
The cerebrum of mammals shares a number of characteristics. In mammals, the septum contains the lateral septal nucleus, medial septal nucleus, nucleus of the diagonal band of Broca, septofimbrial nucleus, and a triangular nucleus. Ascending pathways from the basal ganglia are involved in motor movement in addition to the descending pathways known also in reptiles. In mammals, the archipallium forms the ventromedial portion of the cerebrum, the hippocampal lobe. The paleopallium forms the pyriform lobe which functions in olfaction. Other characteristics of the mammalian cerebrum include the tuberculum olfactorium, internal capsule of projection fibers to the cortex, a fornix which connects the hippocampus to the hypothalamus, and a greater development of the amygdala. Mammalian axonal tracts include the fronto-pontine, occipito-pontine, temporo-pontine, corticospinal, corticobulbar,corticorubral tracts, and association tracts (some of these tracts may be homologous to tracts found in reptiles). In mammals there is an increase in the percentage of ipsilateral optic fibers which do not cross to the opposite side of the brain at the optic chiasm.
Many of the cells which form part of the neocortex circuits specific to mammals also exist in other amniotes (reptiles and birds). Compared to other amniotes, the cells of the developing neocortex in mammals require more time to complete cell divisions and undergo more divisions during a prolonged neurogenetic period. Certain calcium binding proteins (parvalbumin, calbindin, and calretin) are expressed only by certain cells and in distinct layers of the mammalian neocortex.
While the pattern of gyri and sulci may vary between mammalian groups, there are some folds and grooves which are shared. All mammals share a dentate gyrus, a fissure hippocampus, and a fisura rhinalis. The sulcus vallaris of monotremes and marsupials may be homologous to the sulcus genualis in primates and other placental mammals.
Mammals typically possess 4 lobes of the cerebral cortex. These lobes can then be divided into a number of regions, often referred to with the term "cortex". The olfactory cortex contains an anterior olfactory nucleus, the piriform complex, an olfactory tubercle, a cortical amygdale, and an entorhinal cortex. In monotremes, a motor cortex exists in addition to an area of combined motor and sensory cortex. Marsupials have a posterior visual cortex and a lateral auditory cortex.
All mammals seem to share at least 20 isocortex areas, including the primary visual cortex, the primary somatosensory cortex, and the primary motor cortex. In all mammals, V1 projects to V2 and from there to several regions medial and lateral to V2.

Of the class II olfactory genes, several subfamilies of one family have expanded considerably in mammals. Olfactory receptor genes compose about 1% of the mammalian genome with as many as 1,000 receptors. Each olfactory neuron expresses only one allele of one gene, although maternal and paternal alleles are both expressed throughout neuron populations. Mammals can vary considerably in the number of olfactory receptors they possess: dogs possess about 230 million olfactory receptors while humans possess only 10 million.
Vertebrates from lampreys to birds can respond to light (with, for example, changes in circadian rhythms) when both their eyes and pineal organs are removed. Dermal cells in some fish and amphibians can both detect light and initiate changes in pigment dispersal as a result. Mammals are the only vertebrates (with the possible exception of neonatal mammals such as rats) which cannot respond to light without their eyes.
The platypus possesses a prominent nictitating membrane which is reduced in marsupials. Most mammals have a reduced nictitating membrane which is supplied by the abducens nerve when it is present. Nictitating membranes are known from some mammals such as aardvarks, horses, caribou, and some carnivores (such as pandas). Other accessory visual structures unique to mammals include eyelashes, eyebrows, and an orbicularis oculi muscle of eyelids.