the striatum; see section 4.4.4) and Huntington’s chorea (targeting the caudate nucleus;
see section 4.7.8).
The outermost layer of the cerebrum is the cerebral cortex. The 2–5 mm thick mantle
of gray matter that covers the expansive surface of the cerebrum is what makes you
you. The cortex provides the final integration of all neural mechanisms and is a place
where neurotransmitter-influenced bioelectric events are of paramount importance. The
neuroscientist Sherrington vividly described the cortex as “an enchanted loom where
millions of flashing shuttles weave a dissolving pattern.” The cortex is spread over two
cerebral hemispheres, separated from each other by the deep medial longitudinal fissure
but connected to each other by the corpus callosum—a broad band of white matter pro-
viding information relay between the two hemispheres. The cortex is divided into var-
ious lobes that subserve varying functions:frontal(motor),parietal(sensory),occipital
(vision), andtemporal(speech, memory). The hippocampusis an expansion of the tem-
poral lobe and is involved in memory and epilepsy; owing to its importance to memory,
it may be a future design target for anatomically targeted neurologic drugs. Discrete
damage to the cortex can give rise to negative symptoms (i.e., loss of functional abili-
ties produced by a loss of neuronal function) such as apraxia (loss of ability to carry out
purposeful, skilled motor acts despite intact motor systems), alexia (inability to read),
aphasia (inability to speak), and agraphia (inability to write). Focal damage to the
cortex can also give rise to positive symptoms (unwanted, uncontrolled activities pro-
duced by excessive neuronal electrical discharges) in the form of seizures. Epilepsy
(state of recurrent seizures) is a disorder of gray matter, as distinguished from MS, a
disorder of white matter. Global damage to the cortex by neurotoxic substances such as
β-amyloid may lead to neurodegenerative disorders such as Alzheimer’s disease.
The outside of the cortex (i.e., the surface of the brain) is covered by membrane
layers collectively referred to as the meninges. The meninges are trilaminar with the
toughdura materexternally, the delicate arachnoidlining the dura, and the thin pia
mater adhering to the brain. Serotonin receptors within the blood vessels of the
meninges are involved with the mechanism of migraine (section 4.5.5). Infection of
the meninges gives rise to meningitis, which is distinct from an infection involving the
brain,encephalitis(section 9.1). The meninges also extend downwards to encase the
spinal cord in a fluid-filled tube called the thecal sac.
The final part of the brain is the cerebellum. The cerebellum lies attached to the
medulla, pons, and mesencephalon by bands of tissue referred to as cerebellar pedun-
cles. It has an outer layer of gray matter and two hemispheres. As mentioned, the cere-
bellum is involved in the coordination of movement. It is exquisitely sensitive to its
chemical environment. Inebriation with alcohol leads to a staggering gait (ataxia),
reflecting the cerebellum’s response to the excessive amount of ethanol. Many neu-
roactive agents produce cerebellar signs as a first indication of toxicity. For instance,
many anticonvulsant drugs (used for epilepsy, chapter 7) produce the cerebellar sign
callednystagmus—a jerky back-and-forth movement of the ocular pupils. The use of a
rotorod ataxia test(ability of a rodent to stay on a slowly turning rod) is a measure of
cerebellar intactness and can be used as a crude measure of neurotoxicity when evalu-
ating new chemical entities as putative neurologic therapeutics.
The center of the central nervous system is occupied by a system of cavities con-
taining the fluid referred to as cerebral spinal fluid(CSF). The average adult brain
NEUROTRANSMITTERS AND THEIR RECEPTORS 201