Lecture 6 Neurotransmitters

Post-Synaptic Receptor Signaling

• Ionotropic Receptors

• Metabotropic Receptors

Ionotropic “IN” Receptors

• Ion channeling located “in” the receptor (protein) itself

• fast but brief signaling

Every NT have their own

receptors

Metabotropic Receptors

• ion channel located at length from the receptor (protein)

• internal cellular processes required to open

• slower but longer signaling

most common receptors in the CNS

Metabotropic Receptors

Ligand-gated ion channel steps

1. Neurotransmitter binds

2. channel opens

3. ions flow across membrane

G-protein- coupled receptors steps

1. neurotransmitter binds

2. G-protein is activated

3. G-protein activates effector enzymes

4. enzymes uses ATP to activate more proteins (2nd messenger)

5. 2nd messenger proteins activate more enzymes called kinases

6. kinases open ion channels

2 main ingredients to Acetylcholine (ACh)

• Acetyl Co-A

• Choline

Choline Acetyltransferase

makes Acetylcholine (ACh)

ACh Receptors

• Nicotinic

• Muscarinic

Nicotinic is a _____ receptor

ionotropic

Muscarinic is a _____ receptor

metabotropic

ACh Location in the brain

• Cell bodies in nucleus basalis

• Cell bodies in medial septum and diagonal band

nucleus basalis

structure in brain stem

Cell bodies in nucleus basalis

project to cortex

Cell bodies in medial septum and diagonal band

project upwards to hippocampus

ACh Location outside the brain

• Autonomic nervous system

• Neuromuscular junctions

Autonomic nervous system

fight or flight

Neuromuscular junctions

Signals from the brain travel down the spine, signals travel & make connections onto muscles

ACh behavioral functions/disorders

• Learning and memory

• Nucleus basalis of Meynert

Drugs that block off receptors in ACh can affect

learning & memory in ACh

ACh antagonists

Drugs that prevent ACh from binding

Morris Water Maze

• animal model of learning & memory

• ACh would affect it’s spacial learning

Nucleus basalis of Meynert

• Cell bodies produce ACh

• When the cell bodies don’t produce it enough- 1st structure lost in Alzheimers

Nucleus basalis is located

under the frontal cortex

3 monoamine NT

1. Dopamine

2. Norepinephrine

3. Serotonin

2 monoamine NT categories

• Catecholamines

• Indoleamine

Dopamine (DA)

Norepinephrine (NE)

Catecholamines

Serotonin (5-HT)

Indoleamine

Tyrosine Hydroxylase converts Tyrosine into

Dopa

Dopa Decarboxylase converts Dopa into

Dopamine (DA)

Dopamine has _____ receptors

5

Dopamine’s receptors are all

metabotropic

Two enzymes that destroy Dopamine & NE

1. Monoamine Oxidase (MAO)

2. Catechol-O-methyl transferase (COMT)

Psychostimulats in Dopamine

• Cocaine

• Study drugs

• adderall

Neurons get _____ from things we eat like turkey

Tyrosine

Major DA Pathways

1. Nigro-striatal Pathway

2. Mesolimbic Pathway

3. Meso-cortical Pathway

Nigro-striatal Pathway

• loss of DA neurons in sub. Nigra results in Parkinson’s

• Loss of stimulation in striatum

Mesolimbic Pathway

• VTA releases DA into nucleus accumbens

• Reward pathway (pleasure, euphoria)

Drugs if abuse in crease activity in the ____ pathway, giving us a sense of pleasure

Mesolimbic Pathway

Meso-cortical Pathway

• VTA to cerebral cortex

• Also reward pathway

  • more evaluation and motivation to take drugs

Two reward pathways

1. Meso-cortical Pathway

2. Mesolimbic Pathway

What is DA used for?

• Movement (motor)

• Motivation & reward

• Schizophrenia

Movement (motor) effects in DA

• Migro-striatal

• Huntington’s & Parkinson’s

Schizophrenia effects

DA & the frontal cortex

Dopamine converts Dopamine-beta-Hydroxylase into

Norepinephrine (NE)

Norepinephrine (NE) has ______ receptors

5

NE Receptors

• 2 Alpha

• 3 Beta

Major NE Pathways

located in the CNS

Cell bodies of NE

Raphe nuclei inside pons and medulla

Locus Coerules

Densely populated area w/ neurons that produce NE

Locus Coerules project to

• hippocampus

• cortex

• hypothalamus

• thalamus

• cerebellum

• spinal cord

• other forebrain regions

NE Behavioral Effects

• staying focused and on task “attention”

• Cognition thinking process

• Emotional Experiences

Tryptophan Hydroxylase coverts into

Tryptophan

Tryptophan makes

5-Hydroxytryptophan

5HTP Decarboxylase coverts 5-Hydroxytryptophan and makes

5-hydroxytryptamine (Serotonin)

Serotonin has _____ amount of receptors & SUBTYPES

7

What serotonin receptor is inotropic?

3

What destroys serotonin?

MAO

Anti-depressants block what NT

Serotonin

5-HT cell bodies inside the pons

• dorsal raphe nucleus

• median raphe nucleus

Where is serotonin released

• Cortex

• Caudate Putamen

• Nucleus Accumbens

• Thalamus & Hypothalamus

• Limbic system

  • Hippocampus

  • Amygdala

  • Septal Area

Change in serotonin =

change in emotions

5-HT Behavioral functions

• Sleep/wake cycles

• mood

most serotonin is made in the

pons

5-HT Disorders

• Agression

  • lower 5-HT levels correlate into increased aggression

  • Linked to impulsivity

Amino Acids

• Glutamate

• y-amino-butyric acid (GABA)

Glutamate

• Excitatory: Major NT when it binds it stimulates other neurons to be active

Glutamate has ____ Ionotropic (Post-synaptic) receptors

3

what are the 3 gultamate receptors

• Kainate, AMPA, NMDA

Glutamate has ____ metatropic receptors

1-11 total receptors

y-amino-butyric acid (GABA) is inhibitory which means it

stops neuron from being active

y-amino-butyric acid (GABA) has ____ receptors

2

y-amino-butyric acid (GABA) receptors are

1. GABA-A

2. GABA-B

GABA-A is

Ionotropic

GABA-B is

Metabotropic

Amino Acids: Glutamine Synthesis step 1

Astrocytes collects glutamine & sends it to neurons

Glutamine Synthesis step 2

Gultaminase converts glutamine into glutamate

Glutamine Synthesis step 3

Glutamate decarboxylase coverts glutamate into GABA

Glutamate reuptake transportors

• Excitatory amino acid transporters (EAAT)

  • 5 types (EAAT)

Glutamate reuptake step 1

EAAT 1&2 on astrocytes take in glutamate which makes glutamine synthesis

Glutamate reuptake step 2

glutamine synthesis converts glutamate to glutamine

Glutamate reuptake step 3

Glutamine sent to glutamatergic neuron

Glutamate is used extensively in the

frontal cortex - logic reasoning

Cell bodies in cortex project to

striatum

hippocampus

• intra-hippocampus pathways

NMDA antagonist impairs

MWM performance

KO Knockout

dont produce receptors

Over-expression of NMDA receptors produce

Doogie mice

Changes in glutamate

influence schizophrenia

IPSP’S

Inhibitory Post Synaptic Potential

GABA-A

Cl-influx

When chlorine enters the cell of a GABA-A receptors what happens

Charge becomes more negative

When Potassium enters the cell of a GABA-B receptors what happens

Charge becomes more negative

GABA-B

K+ efflux

3 types of GABA reuptake transporters

1. GAT 1

2. GAT 2

3. GAT 3

GAT 1

Both exists on neurons and astrocytes

GAT 2

Astrocytes only

Astrocyte

Degradation takes places

GABA-aminotransferase converts

GABA to Glumate then Glumate converts to glutamine

gultamine gets sent to the neuron for

glutamate and/or GABA synthesis