UNIT 3 SYNAPTIC TRANSMISSION

Site of information transmission from a neuron to another

1 TYPES OF SYNAPSES ACORDING TO THE CELLS INVOLVED

 Synapses between two neurons

 Neuromuscular junction (synapse between a motor neuron and a muscular cell)
 Neuroglandular junction (synapse between neuron and a glandular cell)
2 TYPES OF SYNAPSES ACCORDING TO THE WAY THE INFORMATION IS CONVEYED

Electrical synapses

Electrical signal is transmitted from one neuron to another directly through propagation ions

The channels in the gap junctions

that connect both neurons are
called connexons.

 Virtually no synaptic cleft. Neurons connected by connexons that make up the gap
junctions.
 The message conveyed is exclusively electrical
 Bidirectional transmission
 Quick innate responses, but lack plasticity and cannot sustain learning
Chemical Synapse

Chemical messenger (neurotransmitter) produces changes in membrane potential

 ACTIVE ZONE Part of the presynaptic ending where the neurotransmitters can be
realized

 There is a real synaptic cleft

 The message conveyed is chemical (neurotransmitter)
 Unidirectional transmission
 High plasticity. Allow learning and memory and the ability to adapt to changing
environments
 3 TYPES OF SYNAPSES ACORDING TO CONTATC SITE

Axosomatic synapse

Axon of a cell connects with the soma of another cell

Axodendritic synapse

Axon of a cell connects with the dendrite of another

cell

Axoaxonic synapse

Axon of a cell connects with the axon of another cell

En passant synapse

 Happens with muscles

 It affects a big surface

1 TYPES OF SYNAPSES ACCORDING TO THE POSTSYNAPTIC EFFECT

Excitatory synapses The postsynaptic response consists in a depolarization

 They facilitate action potential generation in the postsynaptic neuron

 Usually, axodendritic synapses

Inhibitory synapse The postsynaptic response consists in hyperpolarization

 They make it more difficult for the postsynaptic neuron to fire an action potential
 Usually, axosomatic synapses

DIA 7
 Exocytosis exit of transmitter molecules
NEUROTRANSMITTER REALISE (EXOCYTOSIS)
1. Action potential occurs
2. Opening of calcium voltage-gated channels
3. Calcium goes in
4. Causes precipitation of vesicles which fuse with the membrane to release neurotransmitters
5. Release of neurotransmitters
6. Binding
7. Inactivation of neurotransmitter

POST SYNAPTIC RECEPTORS

  NT bind onto postsynaptic receptors
 Ligand gated channels open
1. Response depends on the selectivity of the channel for an ion

Receptors can be METABOTROPIC or IONOTROPIC

IONOTROPIC

The receptor protein has an ion channel attached to it

METABOTROPIC
They’re not attached to ion channels. Their activation initiates a biochemical cascade that opens
ion channel

POST SYNAPTIC EFFECTS

Excitatory postsynaptic potential (depolarization) Sodium (N+) goes in, Potassium (k+) goes
out)

Inhibitory postsynaptic potential (hyperpolarization)

1. Potassium (K+) goes out (membrane potential at -80)

2. Chlorine (Cl-) goes in until membrane potential is at -75

Some neurotransmitters can have either excitatory or inhibitory effects

Synaptic integration

Takes place in the axon hillock

 The result of summation determines whether the neuron will fire or not (whether we get
an action potential or not)

SPATIAL SUMMATION All EPSPs and/or IPSPs generated in different postsynaptic terminals reach
the axon hillock at the same time.

TEMPORAL SUMMATION All EPSPs or IPSPs that are produced in the same postsynaptic
terminal reach the axon hillock at different times.
THE ACTION POTENTIAL WILL TAKE PLACE IF THE DEPOLARIZATION CAUSED BY THE EPSP AND IPSP
IS STRONG ENOUGH TO CAUSE A THRESHOLD POTENTIAL

Inactivate the neurotransmitters

Enzymatic degradation: Neurotransmitter molecules are broken down by an enzyme

Reuptake: Neurotransmitter molecules are introduced again into the presynaptic terminal, or into a
glial cell

 Reuptake requires high-affinity active transporters (pumps) in the presynaptic membrane

(or in nearby glial cells)

Reuptake + enzymatic degradation the neurotransmitter goes back to the presynaptic terminal
and there it´s broken down by an enzyme

SYNAPTIC MODULATION

We can modulate the amplitude of EPSP and IPSP by adjusting/altering the activity at the
presynaptic terminal

 EPSP can become more or less intense

 IPSP can become more or less intense
  When there’s too many neurotransmitters, autoreceptors catch them to regulate que
quantity

Autoreceptors ≠ Transport (reuptake) protein

Transport protein (reuptake) inactivates neurotransmitter post synapsis

Autoreceptor Doesn’t have a channel, it holds the neurotransmitter until it needs to be released

 It doesn’t take it inside of the presynaptic terminal

HETERORECEPTORS (axoaxonic synapses)

Presynaptic Inhibition less neurotransmitters

 Less calcium goes in the presynaptic terminal

Presynaptic Facilitation more neurotransmitters

 More calcium goes in the presynaptic terminal

MODULTATION

Neuromodulator  regulates ability of neurotransmitters to open channels

(Neurotransmitter  opens ion channels)

Contrasmitters= Neurotransmitter+ Neuromodulator

MECHANISM OF SYNAPTIC PLASTICITY

 Brain development
 Adaptation to
environment
 Learning and memory

 Neuronal circuits can reorganize as a consequence of experiences

NON-GENOMIC MECHANISMS

Do not involve the synthesis of new proteins, but require modifications of existing proteins

 Lower latency (quick changes)

 Involved in short-term changes (seconds or minutes in duration)

(opening a channel)
GENOMIC MECHANISMS

They involve changes in gene expression (transcription and translation  new proteins are
synthesized

 Higher latency (slow changes)

 Involved in long-term changes (hours, days or years in duration)

1. Protein Kinase activates the enzyme to do the duplication and transcription of DNA
(Transcription Factor)
2. The RNA (copy) goes to Ribosome to be transcribed into a protein
UNIT 4 TRANSMITTER SUBSTANCES

Neurotransmitter

 Sends a message to a nearby cell

 It requires the presence of synapses
 It binds to membrane receptors

Hormone

 Hormones are synthesized by cells of different endocrine glands

 The message can be sent to many cells, some of them located far away
 Hormones are released into the blood stream
 Via the blood stream, hormones can affect virtually any other organ with receptors for the
hormone
 They can have membrane receptors (hydrosoluble) or intracellullar receptors (liposolubles)
LIPOSOLUBLE HORMONES  Act on intracellullar receptors

HYDROSOLUBLE HORMONES Act on metabotropic membrane receptors

ACCORDING TO CHEMICAL STRUCTURE

Protein and peptide hormones Formed by chains of amino acids. For example, the
adrenocorticotropic hormone (ACTH), insulin, or releasing factors.

Steroids Derived from cholesterol (lipid). For example, sexual hormones, and glucocorticoids.

Amines Formed by a modified amino acid. For example, adrenaline, noradrenaline, and thyroid
hormones.

PHARMACHOLOGY Studies the mechanisms of action of a chemical substance and its effects on
the organism

Any substance capable of binding to a receptor in the organism is called LIGAND

THE RECEPTOR IS ACTIVATED, AND A

RESPONSE IS PRODUCED IN THE
POSTSYNAPTIC NEURON

Ligand Receptor Ligand binds to receptor

Endogenous ligand (from the organism) neurotransmitters, hormones…

Exogenous ligand (external agents) drug, toxins…
AGONIST Substance that activates the receptor when it binds to it

 Neurotransmitters are the endogenous agonists of their receptors

 There are drugs that can also act as agonists to specific receptors

ANTAGONIST Substance that prevents the activation of the receptor when it binds to it

 Endogenous antagonists are extremely rare

 Exogenous ligands can act as antagonists to specific receptors

Competitive antagonist

It blocks the entrance of the ligand

to the receptor

MODULATORS

Positive allosteric modulator Increases effect of AGONIST POSTSYNAPSIC RESPONSE IS HIGHER

Negative allosteric modulator Reduces effect of agonist POSTSYNAPSIC RESPONSE IS LOWER

1 EXCITATORY AMINOACIDS (NEUROTRANSMITTERS)
+ +
 Glutamate (glutamic acid) (GLU) EPSPs open Na /K ligand-gated channels
 Aspartate (aspartic acid) (ASP)

THEY ALWAYS HAVE AN EXCITATORY EFFECT ALWAYS CAUSE A DEPOLARIZATION

REUPTAKE there is no degradation

IONOTROCPIC RECEPTORS

NON-NMDA receptors (AMPA and Kainate) EPSP quick response (10-50ms)

Channels Na+, K+

NMDA receptor long duration (200-300ms)

Channels Na+, K+ and Ca2+

Both ligand- and voltage gated Blocked by Mg++ in a voltage-dependent way (blockade
diminiueix progressively as depolarization is produced)
 DUE PLASTICITY

NMDA RECEPTOR AND LONG-TERM POTENTIATION

Increased synaptic response

maintained for a long time, as a
consequence of repeated
stimulation  involves genomic
changes Changes in the
transcription  Morphological
changes

LTP is one of the plasticity

mechanisms involved in memory
consolidation
FUNCTIONAL AND CLINICAL IMPLICATIONS (GLUTAMATE)

Main excitatory NT of the CNS

Learning and memory (LPT)

Development of NS

Excitotoxicity (excess Ca2+ in postsynaptic terminal)

 Brain injury
 Hypoxia
 Hypoglycemia
 Seizures
 Neurodegenerative disorders
 Alzheimer’s disease
2 INHIBITORY AMINOACIDS (NEUROTRANSMITTERS) GABA AND GLYCINE

GABA is the main inhibitory neurotransmitter of the central nervous system

Disorders associated to dysfunction of GABA transmission

 Anxiety disorders
 Epilepsy
 Huntington disease


GABA RECEPTORS

GABA-A Receptor ionotropic (channel and protein together) has a channel for chloride

 Post-synaptic

Benzodiazepines positive modulators of GABA-A receptors (increase the action of GABA)

 They enhance the opening of chloride channel

 Help to induce sleep
 Muscle relaxant
 Anti-seizures

Barbiturates positive modulators of GABA-A receptors (increase the action of GABA)

 At higher doses they can have an effect on their own.

 Main effects: sedation, anaesthesia, epilepsy treatment (anticonvulsants)
GABA-B Receptor metabotropic (channel aside) has a channel for potassium

 Post synaptic or presynaptic

GLYCINE  inhibitory neurotransmitter that we find in the spinal cord

GLYCINE RECEPTORS

Strychnine-sensitive receptor

 Postsynaptic STRYCHNINE: a toxin that

 Ionotropic induces seizures and can be
 Associated to a chloride channel lethal

Non-Strychnine-sensitive receptor

We need this enzyme, otherwise we

3 ACETYLCHOLINE (NEUROTRANSMITTOR)
don’t get acetylcholine
 Muscle contraction
 Excitatory effect (usually)
 Found in the autonomic nervous system

 Inactivation enzyme degradation

RECEPTORS

Agonists Antagonist Curare & Scopolamine

PHARMACOLOGY

Botulinum toxin Does not allow ACH release

Black Widow spider venom  Increases ACH release

ACH EZNYME INHBITION

Means that there’s no degradation of the neurotransmitter, therefore the synapse will go on and n
for a really long time

Reversible Irreversible
 Therapeutic effects.  Highly toxic
 Antidotes of venoms that reduce ACh  Some pesticides
release  Some chemical weapons
 Treatment of first Alzheimer’s disease
stages

FUNCTIONAL AMD CLINICAL IMPLICATIONS

 Attention, Learning and Memory

 REM sleep
 Muscle contraction
 Multiple functions of the autonomic nervous system
 Related to Alzheimer

4 CATECHOLAMINES  DA, NA and ADR

MONOAMINES

CATECHOLAMINES

 Dopamine (dopaminergic neurons)

 Noradrenaline/norepinephrine (noradrenergic
neurons)
 Adrenaline/epinephrine (adrenergic neurons)
* En passant synapse

INDOLAMINES:

 Serotonin
 Histamine
DOPAMINE

LOCATION
RECEPTORS METABOTROPIC

D1 type (D1 and D5)

 Postsynaptic

D2 type (D3, D3, D4)

 Either post- or presynaptic (Autoreceptor)

 Autoreceptors works a mechanism of autoregulation when there’s been a big release
of the neurotransmitter

(Classical antipsychotics are competitive antagonists of D2 receptors and may introduce Parkinson
side-effects)

FUNCTIONAL IMPLICATIONS

 Control of precise movements

 Reward and pleasure
 Attentional mechanisms

CLINICAL IMPLICATIONS

 Addiction
 Schizophrenia
o It can be caused by dopamine decrease or increase
 Parkinson’s disease

NORADRENALINE (NA) AND ADRENALINE (ADR)

LOCATION

In the central nervous system  Locus coeruleus

Periphery  Sympathetic nervous system and Endocrine system

RECEPTORS

- adrenergic

 1 i 2
 Presynaptic (2) and postsynaptic (1)
 Generally, produce inhibition

-adrenergic

 β1, β2 i β3
 Generally postsynaptic, but also presynaptic
 Produce excitation
Receptor agonists

Beta-adrenergic drugs

Receptor competitive antagonists

Propranolol (antagonist of beta receptors)

FUNCTIONAL IMPLICATIONS

 Alertness, sleep/awake cycle

 Stress response
 Mood regulation
 Regulation of memory for emotional events

L-DOPA

 Dopamine precursor
 Used for treating Parkinson’s disease

PSYCHOSTIMULANTS

 Cocaine  Inhibits catecholamine reuptake • Increase arousal

 Amphetamines  Enhances catecholamine release • Decrease fatigue
and reduces catecholamine reuptake • Can induce psychotic events

SEMINAR
Which of the following conditions will most likely lead to nucleus B being inhibited? Justify your
answer.

a) If neuron 1 in nucleus A activates intensely

b) If neuron 2 in nucleus A activates intensely
c) If neuron 1 and 2 in nucleus A activate at the same time.
ANSWER

a) YES! We need to activate neuron 4 previously with an ESPS (action potential needs to happen) for the
axosomatic synapse between neuron 4 and 5 to happen (since it’s axosomatic it Will cause an IPSP)

b) If neuron 2 in nucleus A activates intensely there’s going to be an IPSP in neuron , therefore no action
potential and the signal will not arrive to nucleus B

5 SEROTONIN
En passant synapse

LOCATION

Raphe Nuclei

SYNTHESIS

We need to take it from food

INACTIVATION
 MAO can destroy Serotonin once it
arrives to the pre-synaptic terminal

RECEPTORS

5-HT1 5-HT3 Ionotropic, linked to a Na+-K+ channel

Metabotropic
5-HT2 It will cause an ESPS (cause Na & K are involved)

FUNCTION IMPLICATIONS

 Regulation of sleep and arousal

 Serotonin is a melatonin precursor
 Regulation of food intake
 Mainly for carbohydrates
 Regulation of agressive behaviours
 (low levels of 5-HT related to aggression)
 Regulation of pain transmission

CLINICAL IMPLICATIONS

 Regulation of affective active states

 Monoaminergic hypothesis of depression: deficit of NA and 5-HT, or alterations in
receptors
 Anxiety
 Obsessive-compulsive disorder (OCD)
 Schizophrenia
 Pain Sensation

PHARMACOOLOGY
 MAO inhibitors prevent
the serotonin from being
destroyed at the
presynaptic terminal

SSRIs block the reuptake

of serotonin which
increases the amount
present in the synapse
and magnifies its effects

Ecstasy (MDMA)

 Promotes release of 5-HT (and, to a lower extent, catecholamines)

 In the long-term it may induce degenerative changes in serotonergic neurons
 It may increase chances of depression, memory impairment, etc

Atypical antipsychotics (ex. Clozapine)

Competitive antagonist of 5-HT2A in limbic system, several dopamine receptors, and other
receptors

 Fewer motor side-effects

LSD

Agonist of 5-HT2A receptor  It is a psychedelic drug (induces severe perceptual alterations)