Final Neuro Study Guide

Serotonin/Hallucinogens/Antidepressants

Serotonin (5-HT) is derived from tryptophan

Tryptophan is an amino acid required for the synthesis of serotonin.

• it enters the body through dietary sources, primarily protein-rich foods

  • once ingested, tryptophan is brought to the brain via the BBB to be converted into serotonin

• administering pure tryptophan increases serotonin in the brain

• genetic blocking of the enzyme tryptophan hydroxolase prevents the generation of serotonin

tryptophan gets imported into the nerve terminal, where it eventually is turned into serotonin

• serotonin then gets packaged into vesicles via a transporter called VMAT

• when an AP reaches the terminal, serotonin is released where it can bind to pre/post synaptic receptors

Serotonin is removed from the cleft in two ways:

1. reuptake

2. degradation by monoamine oxidase (MAO)

- Serotonin packaging an release from pre-synaptic terminals, binding to receptors
(pre and post-synaptic) that are neuromodulatory (indirectly increase or decrease
the likelihood of firing an AP)

- Turning off serotonin signals- SERT and MAO- where they are located and what
they do

SERT (Serotonin Transporter) is located on the presynaptic terminal of neurons and is responsible for the reuptake of serotonin from the synaptic cleft back into the neuron. This process effectively terminates the signal of serotonin by reducing its availability in the synapse.

MAO (Monoamine Oxidase) is located within the mitochondria of neurons and astrocytes. It degrades serotonin and other monoamines, contributing to the regulation of serotonin levels in the brain. The major metabolic product of serotonin breakdown by MAO is 5-HIAA.

. Know that 5-HIAA is the major metabolic product of serotonin
breakdown.

• 5-HIAA is a byproduct of serotonin

- Genetic vs. pharmacologic manipulation of the serotonin system.

• genetic manipulation involves altering genes associated with serotonin production or receptor function

• pharmacologic intervention typically involves medication that influences serotonin levels, like SSRIs and MAOIs

- Serotonin impact on aggression- Resident Intruder Test- Depleting serotonin vs
enhancing serotonin synthesis.

• the impact of serotonin on aggression can be tesed using the Resident Intruder test

• The Resident Intruder Test demonstrates the effects of serotonin depletion versus enhanced synthesis

• A resident animal is exposed to an intruder animal, allowing researchers to observe aggressive behaviors as they manipulate the animals’ level of serotonin

  • eliminating serotonin usually leads to a large increase in aggression

  • increasing serotonin decreases aggression

- Serotonin in the gut- Majority of serotonin release-

• 90-95% of serotonin is located in the gut

• altered serotonergic activity in the gut may be one of the leading factors causing IBS

  • IBS-D - serotonin hyperactivity; diarrhea predominant

  • IBS-C - serotonin hyperactivity; constipation predominant

• if we increase or decrease the serotonin too much, the consequences end up extreme

  • a partial agonist seems to be the way to go

- Hallucinogens- Some are naturally occurring while others are synthesized/ Most
act as agonists at the 5-HT2 receptor/ potency can vary widely across different
hallucinogens.

Hallucinogens are drugs causing perceptual or cognitive distortions.

• hallucinogens are either indoleamines or phenylethamines

• they can be found naturally or can be produced in a lab

• most hallucinogens act on the serotonergic system

• potency can vary wildly across different hallucinogens

• most act as agonists on the 5-HT2 receptor

- Hallucinogens can promote synesthetic states in users. Define synesthesia.

Synesthesia: a neurological condition that causes the brain to route sensory information through multiple senses at once

The activation of layer 5 pyramidal neurons in the frontal lobe of the cortex is identified as the primary driver of hallucinogenic states. This activation can occur through direct or indirect mechanisms, influencing the perception and cognitive experience of users.

Assessing Hallucinogenic states:

• the Altered State of Consciousness Scale or ASC and the hallucinogen rating scale are psyhometric measures designed to catigorize and quantify hallucinogens

- Affective disorder- Major depressive disorder (MDD) vs. bipolar disorder

MDD: cyclical episodes of dysphoria and negative thinking (unipolar depression)

Bipolar disorder: cyclical mood swings from depression to mania over time

Both characterized by an exaggeration of mood

- Increase in MDD incidence in the population over the last century

America is seeing a rise in MDD prevalence, and a decrease in age of diagnosis

- How the drug reserpine provided the evidence leading to the Monoamine
Hypothesis for MDD.

Reserpine prevents packaging of certian neurotransmitters (like 5-HT2) leads to depression-like symptoms

the Monoamine Hypothesis was the first to propose a neurochemical basis for mood disorders
- Evidence for the Serotonin Hypothesis for MDD

lower 5-HIAA levels found post-mortem in depressed patients

tryptophan depletion caused by dietary patterns in patients in remission shows increased likelihood of depressive episode relapse

*No direct evidence of 5-HT dysfunction
- Mechanisms for increasing available serotonin in the brain (SSRI and MAOI)
2 main mechanisms:

1. Block reuptake: SERT

2. Block breakdown: MAO

Done by administering SSRIs and MAOIs, respectively

Acetylcholine

- Choline (From diet) and Acetyl CoA (fat and sugar metabolism) as precursors for
Acetylcholine production

• Choline is sourced from the diet

• Acetyl CoA is derived from fat and sugar metabolism

• both serve as necessary precursors for acetylcholine synthesis

  • acetycholine is a crucial neurotransmitter involved in many functions, including muscle control and memory

- How Acetylcholine is released and broken down (acetylcholinesterase) in the
synapse

Acetycholine is released into the synapse, where it binds to receptors. It’s then broken down y the enzyme acetylcholinesterase, which hydrolyzes acetylcholine into choline and acetate, effectively terminating the signal it elicits

- Choline transporter recycles choline back into the presynaptic terminal

The choline transporter is responsible for recycling choline back into the presynaptic terminal after it’s been released and degraded in the synapse

• this recyclying process is critical for maintaining adequate levels of choline for further acetylcholine production

- Nicotinic Acetylcholine receptors vs. Muscarinic receptors

Nicotinic acetylcholine receptors (nAch receptors) are ionotropic and mediate fast synaptic transmissionm while muscarinic receptors are metabotropic, and modulate slower, longer-lasting effects.

Both receptor types respond to the acetylcholine but differ in their mechanisms and functions

- Lower motor neurons are cholinergic (produce and release acetylcholine onto
muscle

Lower neurons are classified as cholinergic because they produce and release acetylcholine into the neuromuscular junction, facilitating communication between the nervous system and muscle fibers, thus enabling movement

- Corticospinal pathway- know where the neurons are located, the
neurotransmitters released

the corticospinal pathway consists of motor neurons located in the motor cortex that send projections down to the spinal cord, where they release neurotransmitters to facilitate voluntary motor control, essentially connecting the brain with the spinal motor circuits

- Neuromuscular junction- Activation of nAch receptors depolarize muscle fibers
leading to action potentials and muscle contraction.

In the neuromuscular junction, activation of nicotinic acetylcholine receptors leads to the depolarization of muscle fibers, resulting in action potential generation and subsequent muscle contraction, a process essential for initiating movement.

- How Botulinum toxin (Botox) and Acetylcholinesterase inhibitors (treatment for
myasthenia gravis) impact cholinergic transmission.

Botox inhibits the release of acetylcholine at the neuromuscular junction, leading to temporary muscle paralysis. acetylcholinesterase inhibitors prevent the breakdown of acetylcholine, enhancing cholinergic transmission

- Acetylcholine and the autonomic nervous system- Sympathetic vs.
Parasympathetic- What neurotransmitters/receptors are used?

in the automatic nervous system, acetylcholine plays a role in both the PNS and the SNS.

• the sympathetic system typically uses norepinephrine, while the parasympathetic system primarily utilizes acetylcholine at its target organs - influencing various bodily functions such as heart rate and digestion

- Basal forebrain cholinergic neurons and their role in sensory perception

Basal forebrain cholinergic neurons are integral to sensory perception and cognitive funtions, as they modulate attention and arousal by releasing acetylcholine to various brain regions, influencing learning and memory processes