NEUROTRANSMITTERS

GLUTAMATE &
GABA

Glutamate
Glutamate is the major
excitatory neurotransmitter in
the brain.
Glutamate is the principal
mediator of sensory
information, motor
coordination, cognition,
emotions and learning.
80-90% of the neurons in the
brain use glutamate to
communicate with each
other.

 Glutamate is synthesized as a step in the

metabolisms of glucose and aminoacids.

 Repolarization from
glutamatergic
activation account for
80% of the energy
expediture of the
human brain.

Glutamate Receptors

 Ionotropic Glutamate receptors are classified in

three: NMDA (N-methyl-D aspartate) linked to
Ca+ entry, AMPA (alfa-amino- 3 hidroxy- 5
methyl- 4 isoxazole propionic acid) and kainate
are permeable to Na+ and K+.

 NMDA receptors are linked to Ca+ entry, AMPA and

kainate are permeable to Na+ and K+.

 Metabotropic
are coupled to
second
messenger
signalling via
G proteins.
mGlu 1 are
coupled to
PLC cascade
and stimulate
calcium
movement.
mGlu 2 and 3
are coupled to
Adenylate
Cyclase.
Both pre and
postsynaptic

 Glutamate is released
from the presynaptic
neuron throgh exocytosis
and binds to ionotropic or
metabotropic, stimulating
cations entrance and
depolarization.
To prevent overstimulation glutamate is
removed by astrocytes
through EAAT (Excitatory
Amino Acids Transporter)
and converted to
glutamine by glutamine
synthetase, released to
the extracellular fluid and
taken up by neurons.

 Glutamine
cycle is the
traffic of
glutamate and
glutamine
between
neurons and
astrocytes.
The trafficking
of glutamate
and glutamine
is the primary
route for
glutamate
recycling.

 To avoid excessive glutamatergic activaction, glutamate has two

transport systems: The vesicular Glutamate transporter (VGLUT)
and the Excitatory Amino Acids Transporter (EAAT).
VGLUT is necessary for glutamate storage in vesicles.

Figure 3. Effect of HCB on neurite outgrowth shown in cells after imunofluorescence. Encapsulated and non-encapsulated
cells were treated with 0.5 nM HCB plus RA (5 mM) as described in Materials and Methods, and then harvested at day 8 for
further differentiation in N2 medium for 2 days, followed by culture in neuronal maturation medium for 4 days in the
presence or absence of 0.5 nM HCB. (A) Inhibition of neurite outgrowth by HCB was observed in GABAergic
(encapsulated) but not in glutamatergic (non-encapsulated) neurons. GABA = GABAergic marker; vGlut = glutamatergic
marker. (B) Quantitation of neurite length by ImageJ demonstrates that HCB induces ~3.5-fold reduction in neurite length in
GABAergic neurons. p < 0.001 by unpaired Students t-test. - See more at: http://www.mdpi.com/16604601/10/10/5244/htm#sthash.WPD2Kcss.dpuf

Glutamate plays an important role during CNS

development, synapse induction, cell migration,
differentiation and death.

 Glutamate
excitotoxicity has
been implicated in
other
neurodegenerative
diseases such as
epilepsy, Alzheimer
disease,
Huntingtons
disease, ischemia
and trauma.

Epilepsy

Gamma Amino Butiric Acid (GABA)

GABA is the main inhibitory neurotransmitter in central nervous

system.
GABAs precursors come from carbohydrates metabolism (Krebs
cycle)

 Glutamate is the precursor for Gamma Amino

Butyric Acid (GABA) in neurons and glutamine in
glial cells.

 Glutamic Acid descarboxylase (GAD) is GABAs

synthesis enzyme. GAD has two subtypes: 65 form
and 67 form.

 GABA receptors
are located in both
pre and
postsynaptic
neurons.
GABA receptors
are transmembrane
proteins.
GABA receptors
can be divided in A,
B and C types.

 GABA A receptor is a heteromeric

structure built by 5 subunits of alfa,
beta and gamma domains.
Chlorine conductance through
GABA A reduces the probability of
action potentials, causing neuronal
inhibition.
GABA A activation inhibits the
release of other neurotransmitters.

 GABA A
receptor is the
target for several
drugs like:
benzodiazepines
,barbiturates,
alcohol and
anesthetics.

Benzodiazepines, Barbiturates & Alcohol

GABA B receptors
Are metabotropic
receptors coupled to G
proteins and similar to
Glut III receptors.
GABA B receptors are
coupled to the
activation of some K+
channel.
They are both in pre
and postsynaptic
neurons.
Presynaptic inhibition
may occur through
GABA B causing
decrease of influx of
calcium.

http://www.wesapiens.org/es/class/2880009/file/18/Sinapsis+en+una+espina+dendr%C3%ADtica

Long Term Potentiation (LTP)

Long Term Depression (LTD)
Learning
Synapse Formation and
removal
Neural Plasticity
Brain remodelling

Neural Plasticity

 Las alteraciones
en la
neurotransmisin
de glutamato est
relacionada con
patologas como
la epilepsia,
accidentes
cerebrovasculares
e hiperalgesia.