5 - Neurotransmitters

what type of neurons are in the dorsal root ganglia?

pseudounipolar

where are chemical synapses located? where are NT synthesized and stored?

end of neuron

axon terminals synthesize NT, they are stored in synaptic vesicles

what does changes in membrane potential depend on?

amount of NT released

amount of transmitter bound to receptors

number of ion channels open

the existing membrane potential

what are postsynaptic potentials caused by? what is dependent on?

channel opening and flow of ions into the cell

receptor-dependent

what is EPSPS and ISPS? what type of channels and transmitters open for each type?

EPSP: depolarization

Na+, Ca++ channels

glutamate, dopamine NT

IPSP: hyperpolarization

Cl- or K+ channels

GABA and glycine, dopamine NT

what are fast/direct and slow/indirect receptors?

fast/direct - change in membrane potential with a synaptic delay between 0.3-0.5 ms

slow/indirect - receptor links to g-proteins, then a messenger system or ion channels. transmitter is often a neuropeptide. process is slow acting and long lasting

how are neurotransmitters cleared?

re-uptake by presynaptic neuron, enzyme degradation, and auto-reception decreasing NT release

what is the difference between electrical synapses and chemical synapses?

electrical synapses have a direct physical connection between pre and postsynaptic neurons. chemical synapses have a space between neurons.

electrical synapses are more rapid via gap junctions - current can flow directly

benefits of electrical synapses is that they are fast, but they can’t go from excitatory to inhibitory so lack flexibility

what is inhibition?

hyperpolarization, reduces the effect of the AP

fewer Ca+ channels open and less NT released

smaller post-synaptic potential

what is facilitation?

depolarization

enhances the effect of the AP

more Ca++ channels open and more NT released

there is a larger post-synaptic potential

A neurotransmitter’s effect is dependent on ______.

receptor

neuromuscular junctions are synapses between? what is the primary NT? what breaks down this NT? what is the primary principle of excitation of a muscle fiber?

somatic motoneurons and skeletal muscle fibers

Ach, acetylcholinesterase

all or none principle - enough NT must be released to meet threshold in order for contraction to occur

what is the excitatory NT at 90% of excitatory synapses in brain?

glutamate (can be in multi, bi, and pseudounipolar neurons)

what receptors are responsible for the bulk of excitatory synaptic transmission in CNS?

AMPA receptors

what happens if glutamate accumulates in EC space after neuronal injury? what are neurologic disorders linked to glutamate?

excessive activation of glutamate receptors leading to neuronal cell death due to excitotoxicity

epilepsy, amyotrophic lateral sclerosis (Lou Gehrig’s disease), schizophrenia, mood disorders

Where is ACh found?

generally excitatory

found in PNS in motor neurons at the NMJ, preganglionic autonomic (both symp and parasymp) neurons and postganglionic parasympathetic neurons

also found in CNS cerebral cortex - basal nuclei, limbic and thalamic regions

what can cause muscle weakness due to failure of transmission of Ach?

botulinum toxin - attacks docking proteins on the presynaptic side interrupting exocytosis

tetanus toxin - a bacteria with an affinity to NMJ. it is taken up by axons and transported to the spinal cord. it is released and taken up by inhibitory interneurons blocking their action. also causes motoneuron hyperactivity

what does acetylcholine do in the PNS and CNS?

generally an excitatory NT in motor regions

plays a critical role in cognition and memory in the CNS

what is excitotoxicity of Ach?

buildup of Ach leads to paralysis by continously exciting the motoneurons

initially violent muscle contractions followed by inability to repolarize cell membranes. progressing to bronchospasm, tachycardia, urination, emesis and shock

where is GABA located? what does it do? what are its pharmacological implications?

chief inhibitory NT in CNS

commonly reduces neuronal excitability by causing hyperpolarization (allowing Cl- in and K+ out)

used to control spasticity, Diazepam, and Baclofen are GABAergic receptor agonists

where is norepinephrine found? what does it do?

originates in the pons and projecting throughout the reticular formation

found in most postganglionic sympathetic neurons except for sweat glands

it is an important ANS NT, generally considered inhibitory but overall effect is general excitement because it inhibits other inhibitory neurons

what are norepinephrine’s effects in the forebrain?

important in the modulation of attention, sleep-wake cycles, and mood

increases arousal and alertness, focuses attentino

increases restlessness and anxiety

what does dopamine do?

it is used by specific cells in the midbrain projecting through the substantia nigra

modulates basal nuclei related circuits - regulates motor function

can be both inhibitory or excitatory depending on the receptor

what happens if you have dopamine deficiency?

movement disorders such as Parkinson’s disease

what is the function of dopamine?

influences mood and emotions through its presence in the hypothalamus and limbic system - mesolimbic pathway

what is the mesolimbic pathway? mesocortical?

mesolimbic: ventral tegmental area (VTA) —> amygdala —> hippocampus

does reward, motivation. excessive dopinergic activity leads to hallucinations of Schizophrenia

mesocortical: VTA —> frontal cortex

does cognitive function, attention, concentration, arousal. dopamine deficiency can cause dyskinesia and Parkinson’s

where is serotonin found?

raphe nuclei of brainstem project widely within CNS - dorsal horns of the spinal cord and the hypothalamus. it is receptor dependent (EPSP/IPSPS) - pain modulation, sleep regulation

what happens if there is dysfunction of serotonergic pathways?

can lead to depression, anxiety, OCD, aggressive behavior and ED

much serotonin is in the GI tract to coordinate gut function

what are neuropeptides? where are they synthesized?

chemical messengers that affect neural activity and other tissues in the body. they are released by neurons and are made up of short chains of amino acids

can be synthesized and packaged in the cell soma

neuromodulatory role modifying the transmission of pain

what kind of receptors do neuropeptides use?

G protein-coupled receptors

beta-endorphin: uses μ receptors that suppress pain released by pituitary in response to pain

enkephalins use μ receptors (endogenous pain relievers similar to morphine)

dynorphin uses κ receptors that reduce pain signals sensitivity to pain)

what is substance P

pain, inflammation, regulation of respiratory and cardiovascular function, GI tract motility

T/F - exogenous opioids use endogenous opioid receptors

T

what are examples of powerful and moderate opioids? what are side effects of opioid use?

powerful (short acting): morphine, meperidine, fentanyl

moderate: codeine, oxycodone

side effects: sedation, euphoria or combative, confusion, nausea and vomiting, orthostatic hypotension, respiratory depression