Neuromodulators Flashcards
Neuromodulators are a set of specific _______ synthesized and released by a specific set of neural _____
neurotransmitters; pathways
Common neuromodulator transmitters include
Dopamine Norepinephrine Epinephrine Serotonin Histamine Acetylcholine
Neuromodulator pathways: each neuromodulator transmitter is synthesized by several small clusters of _____. Most of these clusters are located in the _____. Axons of these neurons project diffusely throughout the brain and ______.
Neurons
brainstem
spinal cord
What is a neuromodulator pathway?
nuclei (groups of neurons) that synthesize neuromodulators
Where are the neurons that synthesize dopamine located? (2)
- Substantia Nigra
2. Ventral tegmental area (VTA)
Where are the neurons that synthesize norepinephrine located? (1)
the Locus ceruleus
Where are the neurons that synthesize serotonin found? (1)
the Raphe nuclei
A scary experience that triggers norepinephrine would activate which neuromodulator pathways?
locus ceruleus
Serotonin is related to sleeping, eating, digesting and overall feelings of well-being and happiness. What neuromodulator pathway is serotonin synthesis found in?
the Raphe nuclei
Dopamine plays a major role in precision of movements (motor function) as well as pleasure, euphoria, compulsion, preservation, reward and addiction. What neuromodulator pathways are dopamine synthesis found in?
- Substantia Nigra
2. VTA (ventral tegmental area)
Acetylcholine has a major function in the parasympathetic nervous system, such as contracting smooth muscle, dilating blood vessels and slowing the heart rate. What neuromodulator pathway is acetylcholine synthesis found in?
Basal forebrain
Where are the neurons that synthesize acetylcholine found? (1)
Basal forebrain
Neurons that synthesize acetylcholine act at the muscarinic ____tropic receptors
metabotropic
Neuromodulators operate almost exclusively through which type of receptors?
G-protein coupled metabotropic receptors
Neuromodulators alter the electrical excitability of many other neural pathways and systems involved in ____, _____ and _____ functions.
sensory
motor
cognitive
Neuromodulator neurons have ____-like properties and fire regular trains of AP due to __trinsic membrane properties
pacemaker
intrinsic
Regular, intrinsic firing patterns of neurons located in the locus coeruleus synthesize which neurotransmitter?
norepinephrine
The firing rate of neuromodulator neurons is further modulated by _____ state
behavioral
Additional changes in firing rate of neuromodulator neurons may be either ___ (steady) or ___ (brief, time-locked to behavioral events)
tonic
phasic
Behavioral states associated w/ change in the level of activity in neuromodulator systems include _____ (reward), _____ (arousal) and __/__ (consciousness)
motivation
attention
sleep/wake
There is a ____ firing rate of noradrenergic neurons in the locus ceruleus associated with waking, conscious state
higher
_____ axons have very specific projections, contacting very few postsynaptic neurons
glutamatergic
____ axons have diffuse projections, contacting MANY postsynaptic neurons
neuromodulator
___ numbers of neurons synthesize and release neuromodulators, yet, have a ___ influence on behavior
few; large
Varicosities of neuromodulator axons are described as
beads on a string
There is a global, ____ release of neuromodulators as the action potential travels down the axon and releases neuromodulators from each ____
diffuse; varicosity
___ neuromodulator receptors influence cortical pyramidal neurons.
multiple
Different receptors act through different ___ proteins
G
There are both ____ and ____ effects on ion channels. The net effect on the neuron depends on which neuromodulator receptors are expressed and the patter of activity in the ______
convergent; divergent
neuromodulator pathways
The dopamine system is implicated in which 3 main clinical applications?
- Parkinson’s
- Addiction
- Schizophrenia
Serotonin and norepinephrine (noradrenaline) systems are implicated in which main clinical application?
depression
Loss of the ascending neuromodulator function can contribute to what major issue?
coma
Histamine is synthesized in the ______ nucleus of the _____
tuberomammillary; hypothalamus
If you began to experience anaphylactic shock from a bee sting, your body would release a ton of histamine to combat the invading toxin. Where would the neuromodulator pathway of histamine be activated?
the tuberomammillary nucleus of the hypothalamus
_____ pathways are dysregulated in schizophrenia and addiction, and originate from the _____
dopamine; VTA
____ neurons die in Parkinson’s disease, and originate from the ____
dopamine; substantia nigra
Axons of which brain system target widespread regions in the brain and spinal cord?
locus coeruleus
The main catecholamines in the brain are ____ and ____
dopamine; norepinephrine
Tyrosine hydroxylase converts tyrosine into ______, which crosses the ____ and is a treatment for Parkinson’s.
L-DOPA; BBB
Dopa decarboxylase converts _____ into ____ which does NOT cross the BBB.
L-DOPA; dopamine
Dopamine b-hydroxylase converts ____ into _____ via one additional step
dopamine; norepinephrine
The primary mechanism of DA/NE is _____
uptake
The secondary mechanism of DA/NE is ____
enzymatic degradation
D1 ____ cAMP whereas D2 ____ cAMP
stimulates; inhibits
For DE receptors, cAMP binds to regulatory subunits on which protein?
Protein Kinase A (PKA)
For NE receptors, b receptors ___ production of cAMP wherease a2 receptors ____ production of cAMP
increase; decrease
Dopamine neurons are ____ when a monkey gets an unexpected reward OR sees a stimulus it has learned to predict rewards for
excited
Dopamine neurons are ____ when a monkey expects a reward but doesn’t get it
inhibited
Reward (prediction error) signal is involved in behavioral reinforcement, ____ and _____
learning
addiction
Norepinephrine neurons have a ___ baseline firing rate when the monkey is drowsy
low
NE neurons have a ___ baseline rate with phasic responses to stimuli when paying attention and ___ in a task
low; engaged
NE neurons have ___ baseline activity without phasic responses when there are alter and ____ tasks
high; switching
Neural activity of NE reflects _____ and _____
attention; arousal
All addictive drugs ____ the DA levels in part of the reward system called the nucleus _____
increase; accumbens
Psychostimulants such as _____ and ______ cause an overall ____ in DA levels
cocaine; amphetamines; increase
Cocaine ____ dopamine transporter (DAT) on the __synaptic DA terminals responsible for synaptic uptake of DA.
blocks; pre
Amphetamine ____ DA from the synaptic vesicles which ___ through DAT back into the synapse.
releases; leaks
Opiates inhibit ______ interneurons in the ____, which suppresses activity of the ____ neurons and increases the firing rate of VTA DA neurons
GABAergic; VTA; GABAergic
_____ influence PREsynaptic terminals to increase DA synaptic concentrations in the nucleus _____
psychostimulants; accumbens
_____ increase the firing rate of DA neurons in the VTA, ___ing synaptic DA concentrations in the nucleus accumbens
Opiates; increasing
Dopamine release is _____ in schizophrenia (SZ) patients
elevated
Drugs that elevate ___ levels, such as amphetamines, can cause psychosis. This is why in SZ, even drug-naive patients experience hallucinations.
dopamine
Genetic linkage studies implicate mutations in genes related to DA neurotransmission in _______
schizophrenia
The clinical efficacy of antipsychotic medications is tightly correlated w/ their ability to bind to which receptors?
D2
Serotonin (5-HT) is synthesized by cell bodies in the _____, and different cortical regions express different 5-HT receptor _____
Raphe nuclei; subtypes
In Depression, there is altered brain activity in the ____ and ____ areas of the brain
limbic; prefrontal
In Depression, there can be changes in the brain’s ____
volume
Antidepressants ___ synaptic concentrations of monoamines ____ and ____
increase; serotonin; norepinephrine
SSRIs are selective serotonin reuptake inhibitors, meaning they ____ uptake
block
MAOIs are monoamine oxidase inhibitors, meaning they ____ degradation
block
Drugs that INCREASE synaptic concentrations of 5-HT will subsequently
elevate mood
