DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

364 system and integrate somatic and vegetative functions, including
those controlling the cardiovascular and gastrointestinal systems.
SECTION II
NEUROPHARMACOLOGY
Limbic System. The limbic system is an archaic term for an assembly
of brain regions (hippocampal formation, amygdaloid complex,
septum, olfactory nuclei, basal ganglia, and selected nuclei of the
diencephalon) grouped around the subcortical borders of the underlying
brain core to which a variety of complex emotional and motivational
functions have been attributed. Modern neuroscience tends
to avoid this term because the ill- defined regions of the “limbic system”
do not function consistently as a system. Parts of these limbic
regions also participate individually in functions that can be more
precisely defined. Thus, the basal ganglia or neostriatum (the caudate
nucleus, putamen, globus pallidus, and lentiform nucleus) form
an essential regulatory segment of the extrapyramidal motor system
that complements the function of the pyramidal (or voluntary) motor
system. Damage to the extrapyramidal system affects the ability to
initiate voluntary movements and causes disorders characterized by
involuntary movements, such as the tremors and rigidity of Parkinson
disease or the uncontrollable limb movements of Huntington’s chorea
(Chapter 22). Similarly, the hippocampus may be crucial to the formation
of recent memory, since this function is lost in patients with
extensive bilateral damage to the hippocampus. Memory is also disrupted
by Alzheimer’s disease, which destroys the intrinsic structure
of the hippocampus as well as parts of the frontal cortex.
Diencephalon. The thalamus lies in the center of the brain, beneath
the cortex and basal ganglia and above the hypothalamus. The neurons
of the thalamus are arranged in distinct clusters, or nuclei,
which are either paired or midline structures. These nuclei act as
relays between incoming sensory pathways and the cortex, between
discrete regions of the thalamus and the hypothalamus, and between
the basal ganglia and the association regions of the cerebral cortex.
The thalamic nuclei and the basal ganglia also exert regulatory control
over visceral functions; aphagia and adipsia, as well as general
sensory neglect, follow damage to the corpus striatum or to selected
circuits ending in the striatum. The hypothalamus is the principal
integrating region for the autonomic nervous system and regulates
body temperature, water balance, intermediary metabolism, blood
pressure, sexual and circadian cycles, secretion from the adenohypophysis,
sleep, and emotion.
Midbrain and Brainstem. The mesencephalon, pons, and medulla
oblongata connect the cerebral hemispheres and thalamushypothalamus
to the spinal cord. These “bridge portions” of the CNS
contain most of the nuclei of the cranial nerves, as well as the major
inflow and outflow tracts from the cortices and spinal cord. These
regions contain the reticular activating system, an important but
incompletely characterized region of gray matter linking peripheral
sensory and motor events with higher levels of nervous integration.
The major monoamine- containing neurons of the brain are found
here. Together, these regions represent the points of central integration
for coordination of essential reflexive acts, such as swallowing
and vomiting, and those that involve the cardiovascular and respiratory
systems; these areas also include the primary receptive regions
for most visceral afferent sensory information. The reticular activating
system is essential for the regulation of sleep, wakefulness, and
level of arousal, as well as for coordination of eye movements. The
fiber systems projecting from the reticular formation have been
called nonspecific because the targets to which they project are relatively
more diffuse in distribution than those of many other neuronal
systems (e.g., specific thalamocortical projections). However,
the chemically homogeneous components of the reticular system
innervate targets in a coherent and functionally integrated manner
despite their broad distribution.
Cerebellum. The cerebellum arises from the posterior pons behind
the cerebral hemispheres. It is highly laminated and redundant in its
detailed cytological organization. The lobules and folia of the cerebellum
project onto specific deep cerebellar nuclei, which in turn make
relatively selective projections to the motor cortex (by way of the
thalamus) and to brainstem nuclei concerned with vestibular function
(position- stabilization). In addition to maintaining the proper
tone of antigravity musculature and providing continuous feedback
during volitional movements of the trunk and extremities, the cerebellum
also may regulate visceral functions (e.g., controlling heart rate,
so as to maintain blood flow despite changes in posture).
Spinal Cord. The spinal cord extends from the caudal end of the
medulla oblongata to the lower lumbar vertebrae. Within this mass of
nerve cells and tracts, sensory information from skin, muscles, joints,
and viscera is locally coordinated with motoneurons and with primary
sensory relay cells that project to and receive signals from
higher levels. The spinal cord is divided into anatomical segments
(cervical, thoracic, lumbar, and sacral) that correspond to divisions of
the peripheral nerves and spinal column (see Figure 8–1). Ascending
and descending tracts of the spinal cord are located within the white
matter at the perimeter of the cord, while intersegmental connections
and synaptic contacts are concentrated within an H- shaped internal
mass of gray matter. Sensory information flows into the dorsal
cord, and motor commands exit via the ventral portion. The preganglionic
neurons of the autonomic nervous system are found in intermediolateral
columns of gray matter. Autonomic reflexes (e.g.,
changes in skin vasculature with alteration of temperature) can be
elicited within local segments of the spinal cord, as shown by the
maintenance of these reflexes after the cord has been severed.
Microanatomy of the Brain
Neurons operate either within layered structures such as the olfactory
bulb, cerebral cortex, hippocampal formation, and cerebellum or in
clustered groupings, defined collections of neurons that aggregate
into nuclei. Specific connections between neurons within or across
the macro- divisions of the brain are essential to the function of the
brain. Through patterns of neuronal circuitry, individual neurons
form functional ensembles to regulate the flow of information within
and between the regions of the brain.
Cellular Organization of the Brain. Present understanding of the
cellular organization of the CNS can be viewed from the perspective
of the size, shape, location, and interconnections between neurons
(Cooper et al., 2003; Shepherd, 2003).
Cell Biology of Neurons. Neurons are classified according to function
(sensory, motor, or interneuron), location, the identity of the transmitter
they synthesize and release or the class or classes of receptor
expressed on the cell surface. Microscopic analysis of a neuron
focuses on its general shape and in particular the complexity of the
afferent receptive surfaces on the dendrites and cell body that receive
synaptic contacts from other neurons. Neurons (Figure 14–1) exhibit