Three types of neurons
From all parts of body to CNS
From CNS to muscle and epithelial glands
Interneurons are neither motor nor sensory. The term is also applied to
brain and spinal cord neurons whose axons connect only with nearby
neurons, to distinguish them from “projection” neurons, whose axons
(projection fibers) project to more distant regions of brain or spinal cord.
Two major mechanisms
Ionotropic = stimulus-gated ion channels
Metabotropic = G-protein complexes
Acetylcholine: Cholinergic transmission
Simple molecule neurotransmitter
Acetylcholine (Ach) is used by all motor axons, autonomic preganglionic neurons,
and postganglionic parasympathetic nerves and by some cells of the motor
cortex and basal ganglia. Ach also functions extensively in the brain to maintain
Depending on the postsynaptic receptor, Ach can be either stimulatory (e.g., at
the neuromuscular junction by motor neurons) or inhibitory (e.g., in
parasympathetic postganglionic fibers to cardiac muscle)
Pathophysiology of cholinergic transmission: myasthenia gravis,
Parkinson disease, Alzheimer dementia
Simple molecule neurotransmitter
Glutamate: glutamatergic transmission; glutamate is the primary stimulatory
neurotransmitter of the brain Gamma aminobutyric acid (GABA); GABA is the primary inhibitory
neurotransmitter in the brain
Pathophysiology: Huntington disease
Glycine; glycine is the primary inhibitory neurotransmitter of the spinal cord
Pathophysiology: Tetanus toxicity
Simple molecule neurotransmitters
These neurotransmitters contain a single amine group in their chemical structure
and include norepinephrine, serotonin, and dopamine.
Neuropeptides alter gene expression → longer duration of action
E.g., Substance P, neuropeptide Y, enkephalins, endorphins, and nitric
Neuropeptides may be secreted at the same time as a small-molecule
neurotransmitter such as norepinephrine (co-transmission). This results in an
immediate, rapid response (because of the smaller neurotransmitter) and a
delayed but prolonged response caused by the neuropeptide.
E.g., glutamate and substance P are co-transmitted in the pain pathway;
glutamate causes immediate inhibition of pain neurotransmission
whereas substance P causes changes in gene expression to produce a
Pathophysiology: Clinical examples
Huntington disease: There is progressive deterioration of the caudate nucleus,
putamen, and frontal cortex, but clinical symptoms do not appear until the fourth
or fifth decade, by which time many patients have already passed on the mutated
autosomal dominant gene to their children. Deterioration starts with
hypertonicity, incontinence, anorexia, dementia, and death. Loss of GABA-
secreting neurons between the striatum and globus pallidus is one of the factors
responsible for the abnormal movements.
Tetanus: Glycine secretion in the spinal cord is inhibited by the tetanus toxin,
exposure to which results in excessive stimulation (dis-inhibition) of the lower
motor neurons, producing spastic muscle contraction (i.e., spastic paralysis).
Nerves must sprout new terminals before the patient can regain normal function.
Depression: The monoamine deficiency theory links depression to a deficiency
in at least one of the three monoamine neurotransmitters: norepinephrine, serotonin, and dopamine. Extensive pharmacologic support for this theory has
been obtained over the years, as evidenced by the efficacy of monoamine
oxidase inhibitors and tricyclic antidepressants, which increase levels of
monoamine neurotransmitters in brain. However, these drugs affect levels of
other neurotransmitters and have numerous side effects. More recently,
serotonin-specific reuptake inhibitors (SSRIs) and non-serotonin-specific
reuptake inhibitors (NSRIs) have been shown to be extremely effective in the
treatment of depression with minimal side effects.
Two types of cells
Connective tissue cells that support neurons
Myelin production: oligodendrocytes in CNS; Schwann
cells in PNS
Blood-brain barrier: astrocytes
Neurons secrete exosomes which may influence synaptic plasticity.
Microglia modulate neurotransmission via shedding microvesicles.
Astrocyte-derived exosomes carry neuroprotective cargo and could contribute to
Neuronal signals trigger exosome release from oligodendrocytes by raising intracellular
Ca -levels. Upon internalization by neurons these exosomes could provide support to
Microglia take up and degrade oligodendroglial exosomes without changing their
inflammatory properties. Under specific pathological conditions these exosomes may
transfer antigens to microglial cells or other APCs and induce inflammatory responses
Nucleus, ganglion and nerve bundle
Nucleus – collection of neuronal cell bodies in CNS
Sexually dimorphic nucleus – appears different in different sexes
Nerve bundle – collection of axons Ganglia – collection of neuronal cell bodies in PNS
The blood-brain (CNS) barrier is a separation of circulating blood from the brain
extracellular fluid in the CNS. It occurs along all capillaries and consists of tight
junctions around the capillaries that do not exist in normal circulation. This barrier also
includes a thick basement membrane of capillary endothelium and astrocytic endfeet.
Endothelial cells restrict the diffusion of microscopic objects (e.g., bacteria) and large or
hydrophilic molecules into the cerebrospinal fluid, while allowing the diffusion of small
hydrophobic molecules (O , 2O , h2rmones). Cells of the barrier actively transport
metabolic products such as glucose across the barrier with specific proteins.
L-DOPA (Levodopa) crosses blood-brain barrier, whereas dopamine itself cannot.
Thus, L-DOPA is used to increase dopamine concentrations in the
treatment of Parkinson’s disease and dopamine-responsive dystonia.
Once L-DOPA has entered the CNS, it is converted into dopamine by the
enzyme aromatic L-amino acid decarboxylase, also known as DOPA
decarboxylase (DOC). Besides the CNS, L-DOPA is also converted into
dopamine from within the peripheral nervous system. The resulting
hyperdopaminergia causes many of the adverse side effects seen with
sole L-DOPA administration. To bypass these effects, it is standard
clinical practice to co-administer (with L-DOPA) a peripheral DOPA
decarboxylase inhibitor (DOCI) to prevent the peripheral synthesis of
dopamine from L-DOPA.
L-DOPA (L-3,4-dihydroxyphenylalanie) is made and used as part of the normal
biology of some animals and plants. Some animals including humans make it via
biosynthesis from the amino acid L-tyrosine. L-DOPA is the precursor to the
neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine
(adrenaline) collectively known as catecholamines. L-DOPA can be
manufactured and in its pure form is sold as a psychoactive drug. As a drug it is
used in the clinical treatment of Parkinson’s disease and dopamine-related
Simple in concept, but challenging to make a therapeutic reality!
Neurons derived from cord-blood cells may represent new therapeutic option
Schwann cells that form myelin sheaths in PNS have an outer cell membrane called
neurilemma, which plays an essential part in regeneration of cut and injured axons.
Axons in the brain and spinal cord have no neurilemma and, therefore, the potential
regeneration in the brain and spinal cord is far less than it is in the PNS. Grafting on a cure – in rats, cells from the peripheral nervous system