Tutoria 1

- A fora
que
faltava
Neuroanatomia
Bsica
MEduarda

QA 1- Qual a constituio de um neurnio? Que tipos de neurnios

existem?

Neurons are the base cellular unit in neuronal tissues, and one of the types
of cells constituting the nervous system. It processes and transmits
information through electro-chemical signals, through synapses small gaps
between a neurons axon and the nexts dendrite.

NOTE: There are exceptions to the above: neurons that lack dendrites, neurons that
have no axon, synapses that connect an axon to another axon or a dendrite to
another dendrite, etc.

A typical neuron consists of a cell body (soma), dendrites, and an axon.

Dendrites: thin structures that arise from the cell body, can branch multiple
times, giving rise to a complex "dendritic tree". Microscopically, they contain
several dendritic spines small protrusions that serve as storage sites for
synaptic strength and electrical transmission, increasing the contact
between neurons;

Axon: special cellular process arising from what is called the axon hillock
a key location for potential generation as it has a higher voltage gated ion
channels than the rest of the neuron;

Soma:

body

of

the

neuron,

contains

the nucleus,

most protein

synthesis occurs here. Gives rise to multiple dendrites and axons;

Axon Terminal: contains the synapses, where neurotransmitters are

released to another neurons dendrite.

Histology and internal structure

In histologic preparations, Nissl bodies can be observed when stained with
basophilic dyes, which reveal the RER and the ribosomal RNA involved in
protein synthesis. The whole soma is supported by neurofilaments, assembled
into neurofibrils; as well as actin and tubulin from microtubules.
Theres a difference in the internal structure of axons and dendrites: the first show
an absence of ribosomes, contrarily to the second.
NOTE: pigments such as neuromelanine and lipofuscin accumulate with age.

Classification of Neurons

Neurons can be classified by the following terms.

Structur
al

Function
al

Polarity

Direction

Other

Action

Discharge
Patterns

Neurotransmitt
er Production

A. Structural classification - Polarity

Unipolar or pseudounipolar: dendrite and axon emerging from same process.
Bipolar: axon and single dendrite on opposite ends of the soma.
Multipolar: two or more dendrites, separate from the axon
Anaxonic: axon cannot be distinguished from dendrites.

NOTE: Further classification of multipolar neurons was proposed by Golgi, whereas

we have:
Type I neurons: neurons with long-projecting axonal processes; examples are
pyramidal cells, Purkinje cells, and anterior horn cells.
Type II neurons: neurons with short axonal processes; the best example is
the granule cell.

B. Structural Classification - Other

Some unique neuronal types can be identified according to their location in the
nervous system and distinct shape.
Examples: Basket cells (form a dense plexus of terminals around the soma of target
cells in the cortex and cerebellum); Betz cells, Lugaro cells (inter neurons of the
cerebellum); Medium spiny neurons (corpus striatum); Purkinje cells (cerebellum,
Golgi I multipolar neuron); Pyramidal cells (Golgi I); Renshaw cells (both ends linked
to alpha motor neurons); Anterior horn cells (motoneurons located in the spinal
cord); Spindle cells ( interneurons that connect areas of the brain).

C. Functional Classification - Direction

Afferent neurons: direction from tissues/organs into the CNS sensory

neurons;

Efferent neurons: from the CNS to effector cells - motor neurons;

Inter-neurons: connect neurons within specific regions of CNS.

D. Functional Classification - Action

The effect of a neuron upon others is determined not by the presynaptic neuron or
by the neurotransmitter, but by the type of receptor that is activated they can be
either excitatory (glutamate, ACh releasing), inhibitory (GABA, glycine releasing) or
modulatory.

E. Functional Classification Discharge Patterns

Tonic or regular spiking - constantly (or tonically) active. Example:

interneurons in neurostriatum.

Phasic or bursting. Neurons that fire in bursts are called phasic.

Fast spiking. Some neurons are notable for their high firing rates, for
example some types of cortical inhibitory interneurons.

F.

Functional Classification Neurotransmitter Production

Cholinergic neurons: Depend on acetylcholine (ACh), a ligand for both ion

channels and muscarinic/nicotinic receptors. Increases the likelihood of an
action potential.
GABAergic neurons: main type of inhibitory neurons, the other being

glycinergic neurons. GABA allows Cl ions, decreasing the probability of an

action potential
Glutamatergic neurons: Glutamate receptors are one of four categories,

three of which are ligand-gated ion channels and one of which is a G-protein
coupled receptor (often referred to as GPCR).
1. AMPA and Kainate receptors both function as cation channels
permeable to Na+ cation channels mediating fast excitatory synaptic
transmission
2. NMDA receptors are another cation channel that is more permeable
to Ca2+. The function of NMDA receptors is dependant on Glycine
receptor binding as a co-agonist within the channel pore. NMDA
receptors do not function without both ligands present.
3. Metabotropic receptors, GPCRs modulate synaptic transmission and
postsynaptic excitability.
Glutamate can cause excitotoxicity when blood flow to the brain is
interrupted, resulting in brain damage, from NMDA and AMPA receptor
activation due to elevated Ca2+ and Na+ entering the post synaptic neuron
and cell damage.

Dopaminergic neurons: these neurons preform both pre and post synaptic
neurotransmission.

Serotonergic neurons: Serotonin (5-Hydroxytryptamine, 5-HT) can act as

excitatory or inhibitory neurons.

QA
2

Como se d a comunicao entre as clulas nervosas? Quais as suas

propriedades fisiolgicas?
Physiological Proprieties

The cell membranes of the axon and soma contain voltage-gated ion
channels that generate and propagate an electrical signal also called
action potential. These signals are sustained by ions like Na+, K+, Cl and
Ca2+. Movement of ions is affected by their concentration gradients.
Stimuli that can activate a neuron: pressure, stretch, chemical transmitters,
changes of the electric potential.

Action Potential

KEY POINTS
Action potential (AP) is a single, transient reversal of membrane polarity. It is
possible to regenerate it and carry it over the nervous system. It follows the all-ornothing principle.

Three phases of AP
1. Depolarization: quick reversal of the polarity to positivity (from -70
mV to +20 mV), through an explosive opening of Na+ channels
(overshoot). Na+ in > K+ out.
2. Repolarization: the membrane potential returns to -70 mV, whereas
Na+ in < K+ out. K+ channels open up slowly than Na+, therefore
they get to their peak after Na+ Ch start closing.

3. Hyperpolarization: K+ channels start closing, bringing the

membrane potential to -90 Mv, and restoring the resting potential.
Proprieties of the AP the initiating current does not affect the duration and
amplitude of AP; neither it declines as it propagates. APs dont overlap, theres a
refractory period.
Thin neurons and axons require less metabolic expense to produce and carry
action potentials, but thicker axons convey impulses more rapidly.

MYELIN SHEATHS ARE ESSENTIAL TO POTENTIAL PROPAGATION

They minimize metabolic expense while maintaining rapid conduction;
Enables PAs to travel faster than in unmyelinated axons;
The PA travels in jumps, from node of Ranvier to node of Ranvier, where
channels are abundant;
The sheaths are formed by glial cells: oligodendrocytes in the CNS and Schwann
cells in the PNS.

SYNAPSES
Structure that permits a neuron (or nerve cell) to pass an electrical or chemical
signal to another neuron. Non-neuronal contacts may be referred to as junctions.

Figure 1 - Events at a synapse

Figure 2 - Types of Synapses

There are two fundamentally different types of synapses:

In a chemical synapse, electrical activity in the presynaptic neuron is

converted into the release of a neurotransmitter to the postsynaptic cell. The
neurotransmitter may initiate an electrical response or a secondary messenger
pathway that may either excite or inhibit the postsynaptic neuron.

Ex:

Chemical

synapses

can

be

classified

according

to

the

neurotransmitter: glutamatergic
(excitatory), GABAergic (inhibitory), cholinergic (excitatory),
and adrenergic (excitatory).

In an electrical synapse, the presynaptic and postsynaptic cell membranes are

connected by special channels called gap junctions, capable of passing electric
current, causing voltage changes.

Chemical Signal vs. Electrical Signal

Ca2+ ions flow

through the
presynaptic
membrane, after
an AP.

Ca2+ sensitive
proteins attach to
NeuTr vesicles

If any, voltage gated

channels open to
depolarization, leading
Ca2+ and H+ ions

NT is released to
the cleft, binding
to receptors

A smaller response in
amplitude is
generated, due to
resistance

The receptor is
activated, the NT
released and
recycled by the PrS
neuron.

Depolarization of PrS
membrane causes a
depolarization of the
PS memmbrane

QA 3- Qual a constituio de uma juno neuromuscular? Que

neurotransmissores operam numa JNM?

QA 4 Como se d a contrao muscular e quais os intervenientes?

QA 5 Descreva o quadro patolgico da miastenia gravis e

estratgias teraputicas.
Myasthenia gravis (MG) is a neuromuscular disorder characterized by weakness and
fatigability of skeletal muscles. The underlying defect is a decrease in the number of
available acetylcholine receptors (AChRs) at neuromuscular junctions due to an
antibody-mediated autoimmune
attack.

PATHOPHYSIOLOGY

Normal Response ACh is synthetized and stored, being released and

combined with the alfa subunits of AChRs on the postsynaptic folds, permitting the
entry of depolarinzing cations on the muscle fiber to trigger contraction. The
process is terminated by AChE and ACh diffusion.

Pathological Response For Myastenia Gravis, AChR are reduced due to autoimmune responses, resulting in a flattening of the synaptic cleft, decreasing

neuromuscular transmission. ACh is still released and triggers a small potential,

which results in weaker muscle contractions.
NOTE: ACh released normally declines on repeated activity (presynaptic rundown) decreased efficiency of neuromuscular transmission combined with the normal
rundown results in the activation of fewer muscle fibers, hence increasing
weakness.
Anti-AChR antibodies reduce the number of available AChRs at neuromuscular
junctions by three distinct mechanisms:
1. Accelerated turnover of AChRs, involving rapid endocytosis of the
receptors;
2. Damage to the postsynaptic muscle membrane by the antibody in
collaboration with complement;
3. Blockade of the active site of the AChR;
ALTERNATIVES: Immune response to muscle-specific kinase (MuSK), involved in
AChR clustering at neuromuscular junctions; Low-density lipoprotein receptor
related protein 4 (Irp4).
The pathogenic antibodies are IgG and are T cell dependent Immunotherapeutic
strategies directed against either the antibody-producing B cells or helper T cells are
effective in this antibody-mediated disease.

SYMPTOMS AND CLINICAL FINDINGS

The thymus is abnormal in -75% of patients ith AChR antibody-positive MG; in -65%
the thymus is "hyperplastic" with the presence of active germinal centers detected
histologically although the hyperplastic thymus is not necessarily enlarged. An
additional 10% of patients have thymic tumors (thymomas). Muscle-like cells within the
thymus (myoid cells) which express AChRs on their surface may serve as a source
of autoantigen and trigger the autoimmune reaction within the thymus gland.