6.13 Neurotransmitters and Neuromodulators

Neuromodulators

When neurotransmitters/messengers elicit complex responses beyond EPSPs and IPSPs, they are referred to as __.

• can modify post-synaptic cell response to dampen/amplify activity

• change presynaptic cell synthesis/release/reuptake/metabolism

Acetylcholine

Synthesized from choline + coenzyme A, cholinergic neurons release __, which are primarily responsible for muscle contractions

[ when bound to | it helps ]

• Nicotinic __ receptors | ionotropic | cognitive functions and behavior

  • agonist: nicotine, plant alkaloid compound in tobacco products

• Muscarinic __ receptors | metabotropic | innervate salivary glands, smooth muscle cells, and heart

  • agonist: muscarine, poison found in some mushrooms

  • antagonist: atropine

Atropine

Naturally occurring antagonist of muscarinic receptors → relax smooth muscles

Found in eyedrops with dilation of pupils

Acetylcholinesterase

Enzyme responsible for the degradation of ACh

Sarin

Nerve gas that inhibits aceylcholinesterase, causing build up of ACh in synaptic cleft

beta-amyloid protein

Mutations of chromosomes 1, 14, 21 lead to __ production associated with neuronal cell death in a severe version of Alzheimer’s Disease, as early 30 years old

Biogenic Amines

Small charged ions synthesized from amino acids + amino groups (NH2)

• catecholamines [dopamine, norepinephrine, epinephrine*]

• serotonin

• histamine

(*) = not a neurotransmitter, but is a major hormone

Catecholamine

A subclass of biogenic amines, __ have a catechol ring and an amine group. They are formed from amino acid tyrosine via:

• uptake of tyrosine → L-dopa

  • conversion by tyrosine hydroxylase

• continual synthesis (in the following order), depending which enzymes are present:

  • 1. dopamine

  • 2. Norepinephrine

  • 3. Epinephrine

Essential for mood, motivation, directed attention, movement, blood pressure regulation, and hormone release

Note: all of their receptors are metabotropic

Monoamine oxidase

Enzyme that breaks down catecholamine neurotransmitters in extracellular fluid and axon terminal

Monoamine oxidase inhibitors

Drugs that increase amount of norepinephrine and dopamine via slowing down their metabolic degradation

Adrenergic

__ is used to describe neurons that release/receptors that bind norepinephine or epinephrine

• alpha-__ receptors

  • A2 = presynaptically inhibits norepinephine release

  • A1 = postsynaptically stimulates/inhibits K+ channels

• beta-__ receptors

  • increases cAMP via Gs proteins

  • B1, B2, B3

Serotonin

Also known as 5-HT, it is produced from tryptophan (essential amino acid)

• excites muscles and inhibits pathways mediating sensation

• lowest during sleep / highest when awake

• regulates food intake, reproductive behavior, mood + anxiety

Paxil

__ (peroxetine) and Lexapro (escitalopram) inactivates presynaptic membrane 5-HT transporter reuptake → increases serotonin in synapses → aid treatment of depression

associated with decreased appetite but increased weight gain (disrupts enzymatic pathways that fuel metabolism, 90% being in digestive system)

LSD

Lyseric acid diethylamide. Alters 5-HT receptor → 5-HT2A receptor in brain. This leads to hallucinations

Glutamate

Excitatory amino acid. Major neurotransmitter in CNS (interacts with 50% of excitatory synapses)

Has ionotropic receptors:

• AMPA = depolarizes w/ Na+ influx

• NMDA = increases Ca+ uptake

  • as it is blocked by Mg ion MUST reach specific depolarized state first to displace it + be open

Plays important role in Long Term Potential: major cellular process involvee in learning memory, as NMDA opens much quicker the more its AMPA is activated (mirrors our process of internalizing info better w/ repetition)

excitotoxicity

Phenomenon where injury/death of brain cells rapidly spreads to adjacent regions. NMDA receptors are associated with this when glutamate-containing cells rupture and lead to overstimulation of NMDA receptors such that an unhealthy Ca2+ influx occurs → kills/ruptures those neurons as well

GABA

Major inhibitory neurotransmitter in brain. Modified form of glutamate (amino acid)

• Inc. Cl- influx → hyperpolarizes cell

• has ionotropic and metabotropic receptors

Xanax

__ (alprazolam) alongside Klonopin (clonazepam) acts as agonists to GABA and increase Cl- influx

• reduces anxiety

• guards against seizures

• induces sleep

ethanol

Synapses that use GABA are also among the many targets of __ (ethyl alcohol) in alcoholic beverages.

• stimulates GABA synapses

• inhibits excitatory glutamate synapses

reduces activity of brain → sensory perception (hearing and balance) inhibition, loss of motor coordination, impaired judgement, memory loss and unconsciousness

• Dopaminergic and endogenous opioid signaling are also affected → short-term mood elevation and euphoria

Glycine

Major inhibitory neurotransmitter in spinal cord and brainstem.

• Increases influx of Cl-

• Essential for maintaining excitatory and inhibitory activity in spinal cord integrating centers

Strychnine

Antagonist of glycine receptors. Leads to hyperexcitability throughout nervous system

• convulsions

• spastic contraction

• skeletal muscles

• even leads to death w/ impairment of respiratory muscles

Neuropeptides