Basic Neurochem

In which direction does communication between neurons typically occur?

Transmission occurs in one direction from the presynaptic to the postsynaptic neuron (left to right).

Concept: Axodendritic Synapse

Definition: A synaptic connection between the axon of a presynaptic neuron and the dendrite of a postsynaptic neuron.

Concept: Axosomatic Synapse

Definition: A synaptic connection between the axon of a presynaptic neuron and the cell body (soma) of a postsynaptic neuron.

Concept: Axoaxonic Synapse

Definition: A synaptic connection between the axon of a presynaptic neuron and the axon of a postsynaptic neuron.

Axo__ arragement allows for presynaptic _ or presynaptic _ based on if the presynaptic neuron is inhibitory or excitatory.

axonic; inhibition; facilitation

What event triggers the opening of voltage-gated Ca2+ channels in the presynaptic terminal?

The arrival of an action potential and the resulting depolarization of the membrane.

How does Ca2+ entry into the presynaptic terminal facilitate neurotransmitter release?

Ca2+ causes synaptic vesicles to fuse with the terminal membrane and release their contents via exocytosis.

What is the primary function of neurotransmitter binding to (inhibitory or excitatory) postsynaptic receptors?

It causes the opening or closing of postsynaptic ion channels to change the excitability of the cell.

The process of retrieving vesicles from the plasma membrane after neurotransmitter release is known as _____.

Endocytosis

Synaptic/NT transmission cannot happen w/o . However, can still happen.

Ca2+; Action Potentials

Amount of NT released depends on _ of _ in the presynaptic terminal, which increases w/ the duration and frequeny of AP.

concentration; Ca2+

NT interact w/ postsynaptic receptors including _ and can trigger _ or __, then cascade commence again int he new postsynaptic neuron.

membrane permeability; EPSPs; IPSPs

What are the two primary mechanisms for neurotransmitter inactivation after release?

Reuptake by transporters and enzymatic breakdown.

Where are reuptake and enzyme molecules? (aka How to inactivate a neurotransmitter?)

"Reuptake = presynaptic terminal & Glial cells

Enzyme breakdown = Postsynaptic terminal"

What are the 5 criterion to be considered a NT?

Be synthesized and stored in the neuron

Be released from the neuron upon electrical stimulation

Have postsynaptic receptors

Be deactivated after release and action

Have selective inhibitors

What is the difference between presynaptic inhibition and presynaptic facilitation?

Inhibition involves a decrease in neurotransmitter release, while facilitation involves an enhanced release caused by another neuron.

Concept: Autoreceptors

Definition: Receptors on the presynaptic terminal that, when stimulated by the released neurotransmitter, decrease subsequent neurotransmitter release.

What are the two receptor superfamilies?

"Ionotropic receptors and Metatropic receptors"

Characteristics of Ionotropic receptors

Ligand-gated channels; FAST; short-lasting; made of several subunits; NOT coupled to second messengers; intrinsic ion channel that opens in response to NT or drug (at rest, its closed)

Characteristics of Metatropic Receptors

G protein-coupled receptors; only 1 subunit; activate G proteins in response to NT or drug; SLOWER; longer-lasting; does not possess a channel or pore

Small Molecule > Amino Acid > __ hint: function as NT

Glutamate, GABA, and Glycine.

Small Molecule > Biogenic Amines > __

Catecholamines and Indolamines.

Small Molecule > Biogenic amines > Catecholamines > __

Dopamine, Norepinephrine, and Epinephrine.

Dopamine and Norepinephrine are also considered __ b/c they have excitory and inhibitory qualities.

modulators

Small Molecule > Biogenic amines > indolamines > __

Serotonin (5-HT) and Histamine.

Small molecule > Purines (that act as neurotransmitters) > __

ATP and Adenosine.

Where are small molecule NT synthesized?

Terminal efficient and retrograde (soma → terminal)

How do neuropeptides generally differ from small-molecule neurotransmitters in terms of molecule size and action speed?

Neuropeptides are large molecules with slower action and modulatory effects.

Where are neuropeptides synthesized?

Soma

Name two unconventional gasotransmitters identified in the source.

Nitric Oxide (NO) and Carbon Monoxide (CO).

How do gasotransmitters differ from conventional neurotransmitters regarding storage and signaling direction?

They are not stored in vesicles, diffuse freely, and can participate in retrograde signaling.

Orphan Receptors

Substance w/ a receptor but we don’t know the thing that binds to it.

What are the two Ach receptor subtypes?

Nicotinic (excited) and Muscarinic (rest)

Describe Nicotinic receptors.

Consists of 5 subunits and is ionotropic (ion channel)

Why does nicotine affect the brain but not muscle nicotinic receptors?

The receptors have different protein motifs, making brain receptors sensitive to nicotine and muscle receptors insensitive.

What ion flow occurs when acetylcholine binds to a nicotinic receptor?

Na+ and Ca2+ ions enter the cell, leading to membrane depolarization.

Identify the brain regions where high levels of muscarinic receptors are found.

Neocortex, hippocampus, thalamus, forebrain, striatum, basal ganglia;

striatum important to motor function,

neocortex and hippocampus = important to cognitive function

Describe Muscarinic receptors.

All metabotropic, M1-M5, have a direct and indirect second-messenger system

Describe the direct and indirect muscarinic receptor process.

Direct: G protein activates G protein-gated channel; Indirect: G protein activates enzyme (second-messenger), and then channel activates (takes longer)

Regarding Muscarinic receptors, the direct pathway only has a __ messenger, which is __. The Indirect pathway has also a __ messenger, which is __.

1st; Extracellular (outside); 2nd; intracellular (inside).

What is the general functional role of muscarinic receptors in the neocortex and hippocampus? Compare to that in the striatum.

They play an important role in cognitive function, whereas those in the striatum are involved in motor function

Which enzyme is responsible for the degradation of acetylcholine (ACh)?

Acetylcholinesterase (AChE) => allow relaxation => needs to work all the time to prevent overstimulation from Ach

How does botulinum toxin (Botox) cause muscle paralysis?

It blocks AChE, causing a buildup and muscle overstimulation => muscular paralysis

Name clinical disorders characterized by involuntary muscle contractions that can be treated with botulinum toxin.

Strabismus (crossed eyes), hemifacial spasms (spasms on one side of face), dystonias (prolonged muscle contraction)

What is the pharmacological effect of nerve gases like Sarin and Soman?

They are toxic, irreversible inhibitors of the enzyme acetylcholinesterase (AChE).

What is the clinical use for reversible acetylcholinesterase inhibitors?

They are used as cognitive enhancers to delay the decline in function in Alzheimer’s Disease patients.

Describe Tyrosine to NE process.

Tyrosine → DOPA by TH; DOPA → Dopamine by AADC; Dopamine → NE by DBH

After synthesis, catecholamines are transported into __ for later release.

Synaptic vesicles.

What enzyme is primarily responsible for the degradation of catecholamines and serotonin?

Monoamine Oxidase (MAO)

What is the rate limiting enzyme for tyrosine to NE?

Tyrosine Hydroxylase (TH) determines the ammount of dopamine or NE formed

How many main subtypes of dopamine receptors exist, and what receptor superfamily do they belong to?

There are five main subtypes (D_1 through D_5), all of which are metabotropic receptors.

Which dopamine receptor subtypes belong to the D_1 family?

D_1 and D_5. Excitatory

Which dopamine receptor subtypes belong to the D_2 family?

D_2, D_3, and D_4. Inhibitory

Concept: Nigrostriatal Pathway

Definition: A dopaminergic pathway that projects from the substantia nigra to the striatum. A9. Damage => motor disorders/parkinson's

Concept: Mesolimbic Pathway

Definition: A dopaminergic pathway that projects from the ventral tegmental area to limbic regions. A10. Damage => mood and emotional disfunction

Concept: Mesocortical Pathway

Definition: A dopaminergic pathway that projects from the ventral tegmental area to the cerebral cortex. A10. Damage => ADHD or schizophrenia

What behavioral role is specifically associated with noradrenergic neurons in the locus coeruleus (LC)?

Vigilance (Resting = NE not active)

If someone has anxiety or PTSD, Noradrenergic neuron activity would be __.

High

From what dietary precursor is serotonin synthesized?

Tryptophan

Describe the mechanism for Tryptophan to serotonin

Tryptophan → 5-HTP by Tryptophan hydroxylase; 5-HTP → 5-HT (serotonin) by L-amino acid decarbosylase.

What is the rate limiting enzyme for Tryptophan to Serotonin?

Tryptophan hydroxylase determines the amount of 5-HT formed.

While most serotonin receptors are metabotropic, which subtype is an ion channel (ionotropic)?

5-HT_3

Why is the 5-HT_2B receptor nicknamed the "death receptor"?

Drugs that stimulate this receptor cause heart problems.

Which amino acid is the most abundant in the brain and serves as a major excitatory neurotransmitter?

Glutamate

What immediate precursor is converted into glutamate by the enzyme glutaminase?

Glutamine

What are the two glutamate receptor subtypes?

Ionic and metabotropic

Describe NMDA receptors

Glutamate receptor subtype; ionotropic receptor that can directly activate a second messenger system by allowing Na+ and Ca2+ in?

Which two glutamate receptor subtypes are often referred to as "non-NMDA" receptors?

Kainate and AMPA receptors.

What is the unique function of GABA compared to glutamate's metabolic roles?

The only function of GABA is to serve as a neurotransmitter.

By what biochemical step is GABA synthesized from glutamate?

By the action of the enzyme glutamic acid decarboxylase (GAD).

Describe GABA_A

Inotropic, produces a fast inhibitory response and is the target of alcohol, benzodiazepines, and barbiturates. It allows Cl- in => induce inhibition => someone that’ stressed would like a drink.

What is the structural classification of the GABA_B receptor?

It is a metabotropic receptor and allows a slow inhibitory response.

Name four brain regions with high concentrations of nerve terminals that use GABA.

Cerebral cortex, hippocampus, cerebellum, and substantia nigra.

How do ionotropic receptors compare to metabotropic receptors in terms of response speed and duration?

Ionotropic receptors work very fast, while metabotropic receptors respond more slowly but have longer-lasting effects.

5-HT cell body location?

Raphe Nuclei

Glutamate EPSPs are mediated by __ receptors

AMPA

How is ACh synthesized?

Ach synthesized in cytoplasm of nerve terminals from choline and acetyl-CoA by the enzyme choline acetyltransferase

What would happen if ACh is not broken down immedently after release via enzymes?

Muscle spasms

Steps 1-5 of synaptic transmission

1) NT synthesized and stored

2) AP

3) Depolarization: Ca2+ channels open

4) Ca2+ enters

5) Ca2+ causes vesicles fuse to membrane

Steps 6-10 of synaptic transmission

6) NT released (exocytosis)

7) NT binds to postsynaptic receptos

6) Opening o closing of postsynptic channels

9) Postsynaptic current excits or inhibits postsynaptic potential to change excitability

10) Retrieval of vesicles from plasma membrane (endocytosis)