Exam1Lec6NeurochemicalCircuitry Flashcards
What is the main purpose of a neuron?
to communicate, each neuron is connected. to up to 10,000 other neurons
What is synpatic transmission?
Process by which a neuron communicates with a target cell across a synapse
chemical transmission – involves neurotransmitter release
direct contact – can be electrical or involve protein-protein interactions
For chemical synapses the synpatic cleft is much ____ than at electrical synapses.
larger
Chemical synapses involves ____ neurotransmitter release
calcium-dependent neurotransmitter release
Definition of neurotransmitter
an endogenous substance that is released from a neuron and acts on a receptor site to produce a functional change in the properties of the cell on which the receptor is located
Life Cycle of Conventional Neurotransmitters
5:40
What are 4 characterristics of neurotransmitters that are gases such as NO and CO?
- Not present or stored in vesicles
- Not released from nerve terminals by exocytosis
- Too small to have recedptors
- Synthesized (through enzyamtic rxns) and releases upon demand through diffusi9on
Does neurotransmitter gases such as NO and CO do retorgrade or anterograde signaling?
Retrograder signaling from postsynaptic cells back to pre-synaptic terminals
What is the primary action of neurotransmitters NO and CO?
primary action is to increase cGMP, activating cGMP-dependent protein kinases (PKG), which phosphorylate several substrates including regulators of calcium homeostasis, calcium sensitivity of cellular proteins, platelet activation and adhesion, smooth muscle contraction, cardiac function, and gene expression.
How is NO synthesisized?
NO is synthesized from arginine via NO synthase (NOS)
How is NO regulated and how does it signal?
Neuronal NO is regulated by Ca2+ binding to calmodulin, a Ca2+ sensor protein
Quickly signals, since NO quickly decays due to spontaneously reacting with oxygen
not stored in muscle, used immediately
How is CO synthezised?
CO is synthesized from heme by heme oxygenase (HO), which catalyzes the conversion of heme to biliverdin, liberating CO
CO is the main regulator of what? and how does it signal?
CO is a main regulator of cGMP in the brain – mediates smooth muscle relaxation
Quickly signals, since CO quickly decays due to spontaneously reacting with oxygen
What are 2 examples of growth factors as neurotransmitters?
BDNF and NGF (neurotrophins)
How are growth factor neurotransmitters synthesized and released?
these proteins are constitutively synthesized & released from soma and dendrites and synthesized & released from soma, dendrites and nerve terminals upon neuronal depolarization
can continuasly be expressed and released as needed. also can be regulated as needed where they are packaged and stored as vesicles and released upon dep
What does neurotrophin signaling mediate?
mediated by interactions with neurotrophin receptors, which can be both high affinity (Trk) and low affinity (p75NTR), and are involved with activating major signaling pathways affecting neuronal survival and function
What are the effects of Brain-derived neurotrophic factor (BDNF)?
survival and growth of neurons neurogenesis
influences excitabiloty and brain connectivity.
What occurs if you have too much and too little BDNF?
Too much:: affects plasticity and
may affect learning
Too little: affects plasticity and linked to increased depressive episode
Modulating neurotransmission
Normally: endogenous ligand binds to receptor and receptor is activated
Agonist drug: acts binds to receptor and acts jsut like a neurotransmitter
Antagonist drug : binds at the receptir site, but wont have an action, and the receptor can’t be activated
How is ACh synthesized?
synthesized from choline and acetyl CoA by the enzyme choline acetyltransferase (ChAT)
What is the rate-limiting step of ACh metabolism?
rate-limiting synthetic step is high affinity choline uptake (Na+ dependent); ChAT is not rate-limiting
NOT THE ENZYME
How is ACh signal terminated?
Action terminated: hydrolysis by acetylcholinesterase (AChE)
turns back into choline and acetic acid. Choline can be recycled and used again to make ACh.
What is the effect of ACh?
Involved in muscle movement as well as neuronal plasticity and memory
What happens if you have too much and too little ACh?
Too much: muscle contractions (e.g. black widow venom)
Too little: paralysis (e.g. curare and botulism toxin)
cholinergic circuits
What are the two major groups of projections? (where do neurons originate?)
basal forebrain neurons
brainstem neurons
Where do basal forebrain neurins project into?
said we dont need to know
basal forebrain neurons
* projects into the neocortex, basolateral amygdala, olfactory bulb, hippocampus and entorhinal cortex
* important for cortical activation, cognitive function and memory processing
* degenerate in Alzheimer’s disease
Where do brainstem neurons project into?
said we dont need to know
brainstem neurons
* primarily project into the thalamus, but can also project to the basal forebrain
* activation induces REM
How is serotonon (5-HT) synthesized and transported?
Synthesized from tryptophan with tryptophan hydroxylase (rate limiting)
transported into vesicle by VMAT2
How is serotonon (5-HT) terminated and catabolized?
terminated by re-uptake into pre-synaptic terminals
Catabolized by MAO-A
serotinon has its own transporterf where it can get re-packages into the pre-synaptic cell and terminate signal in synaptic cleft
MAO-A enzyme breaks down serotonin in synaptic cleft.
What are the indicated effects of serotonin?
Important in mood control, circadian rhythms, motor behaviors, appetite, digestion (90% of serotonin is found in the intestine) and state of mental arousal
What happens if you have too much and too little serotonin?
Too much: Serotonin syndrome: confusion, twitching and trembling, dilated pupils, shivering, goosebumps, headache, sweating and diarrhea, irregular and fast heartbeat
Found in wasp stings and scorpion venom
Too little: Mental health symptoms, sleep changes SCHIZOPHRENIA
serotonergic circutis
Where does serotonin orginate?
In the raphe nuclei ( has 2 nodes, rostral and caudal)
Where do rostral raphe nuclei project to?
cortical projections - sensory processing; hyperactive in schizophrenia
hypothalamic projections - homeostasis
limbic projections - depression
Where does caudal raphe nuclei project?
project to spinal cord – regulates motor and non-motor function
What is the medical use of SSRI’s? what is the mechanism of action?
Medical Use
Depression and panic attacks
Mechanism of Action
Serotonin reuptake inhibitor (SSRI)
maintin signlaing longer
What is the main effect of SSRI’s? what are the side effects?
Main Effect
Improve mood, sleep, appetite and energy level
Side Effects
Nausea, headache, drowsiness, anxiety, trouble sleeping, sexual problems
How is Dopamine synthesized?
synthesized from tyrosine with tyrosine hydroxylase (TH) (rate-limiting enzyme)
How is dopamine transported?
transported into vesicle by the vesicular monoamine transporter VMAT2; driven by H+ gradient
How is Dopamine terminated?
following release, action terminated by reuptake into presynaptic terminals
can also be taken up postsynaptically
terminated by both post and pre-synaptic
What are the indicated effects of Dopamine?
Important in modulating movement and reward motivation, compulsion, perseverance
Motor function (fine tuning) - inhibit unwanted movement
What happens if you have too much and too little Dopamine?
Too much: schizophrenia
Too little: Parkinson’s disease
Where does Dompaminergic neurons originate from?
Basal ganglia ( ventral tegmental area (VTA) and substantia nigra)
Which neurotransmitter is responsible for liking?
Serotonin:
mood stabilixer, wellbeing,happiness
Which neurotransmitter is responsible for wanting?
Dopamine: motivational role in brain’s reward system
How is norepinephrine synthezised?
synthesized from tyrosine with tyrosine hydroxylase (TH) (rate-limiting)
both dopa and nor epi are sytntheiszed from same precursor bc dopa turns into norepi
How is norepinephrine transported?
DA transported into vesicle by VMAT2 followed by dopamine β-hydroxylation (DßH) to NE
How is norepinephrine terminated and catabolized?
following release, action terminated by reuptake into presynaptic terminals
catabolized by MAO-A and COMT
What are the indicated effects of norepinephrine?
Influences sleep and wakefulness, alertness, arousal, and readiness for action.
What happens if you have too much and too little norepinephrine ?
Too much: increased blood pressure, anxiety, sweating, headaches
Too little: lethargy, lack of focus
Where do noradrenergic neurons originate?
locus coeruleus and lateral tegmental nuclei
What are the medical uses and mechanism of action of SNRIs?
Medical Use
Depression, anxiety, chronic pain
Mechanism of Action
Serotonin and norepinephrine reuptake inhibitors (SNRIs)
What are the main effects and side effecrs of SNRIs?
Main Effect
Improve mood, lower anxiety, lower nerve pain
Side Effects
Nausea, headache, drowsiness, dry mouth
How is glutamate synthesized and transported?
synthesized from glutamine via rate-limiting glutaminase
transported into vesicle by VGLUT
How is glutamate terminated?
action terminated by sodium-dependent uptake into neurons and astrocytes by excitatory amino acid transporter (EAAT) followed by catabolism
What are the indicated effects of glutamate?
Main excitatory neurotransmitter
Role in synaptic plasticity, learning and memory
Important role in seizures
What happens if you have too much and too little glutamate?
Too much: excitotoxicity and seizures
Too little: psychosis, coma and death
Where do glutamatergic neurons originate?
widespread throughout CNS,
mediate fast excitation in CNS.
NMDA receptor antagonists may be neuroprotective—basis for use in AD & PD; may play role in schizophrenia
Where is GABA synthesized and how is it transported?
synthesized from glutamate by rate-limiting glutamic acid decarboxylase (GAD) in CNS and retina
transported into vesicle by VGAT
How is Gaba terminated?
action terminated by sodium-dependent GABA transporter (GAT) into neurons and astrocytes and catabolized by GABA-T (GABA transaminase)
What are the indicated effects of GABA?
Main inhibitory neurotransmitter
Important in motor control and vision
Plays important role in seizures, anxiety, & insomnia
Plays a role in pain
What happens if we have too much and too little GABA?
Too much: over-sedation, over-relaxing of muscles including the heart and respiration
Too little: Anxiety and seizures
Where do GABAerigic neurons originate?
widespread throughout CNS, represent abt 40% if all neurons in the brain
Baclofen (lioresal)
Medical use ?
Mechanism of action?
Medical Use
Muscle stiffness and tightness from multiple sclerosis or spinal cord injury
Nerve pain
Mechanism of Action
Agonist on GABAB receptors
baclofen is a muscle relaxant
Baclofen (lioresal)
Main effect
Side effects
Main Effect
Relax muscles, improves movement and relieves pain
Side Effects
Drowsiness, weakness, confusion
Ketamine
Mechanism of Action
low yield
Mechanism of Action
NMDA receptor antagonists
ketamine is an anesthetic
Ketamine
main effects and side effects
Main Effect
Numbing of pain and sedation, feeling of distance from body
Side Effects
Nausea, vomiting, coma
ketamine is an anesthetic
Similar drugs: phencyclidine (PCP) and nitrous oxide (N2O)
Gas neurotransmitters are ____ while growth factor neurotransmitters exhibit both ____.
synthesized and released on demand
constitutive and activity-dependent release.
____ cholinergic neurons play a major role in ____ and degenerate in ____.
Basal forebrain, neuronal plasticity, AD.
____ neurons play a major role reward behavior. ____ DA neurons degenerate in ____.
VTA DA, Substantia nigra, PD
Serotonin neurons originate primarily from the ____ and also have widespread projections. These neurons play important roles in ____.
raphe nucleus, mood control and depression
Noradrenergic neurons originate primarily from the ____ and have widespread projections. These neurons play important roles in ____, ____, and ____.
locus coeruleus, attention, homeostasis, and depression
Glutamate pathways are also widespread throughout the brain and play important roles in ____, ____, ____, and perhaps ____ through excitotoxicity.
widespread
synaptic plasticity,
learning and memory,
seizures,
neurodegeneration
GABA pathways are ____ throughout the brain and play an important role in ____ and ____ disorders.
widespread, anxiety, seizure
Neurotransmission can be altered by drugs that ____ neurotransmitters,____ neurotransmitters from interacting with receptors, and ____ neurotransmitter reuptake
mimic, block, prevent
