neurotransmitters

Question 1

overview of direct synaptic transmission

Answer 1

neurotransmitter release -> receptor binding -> ion channels open or close -> conductance change causes current flow -> postsynaptic potential changes (EPSP or IPSP) -> summation and threshold -> action potential or no action potential

Question 2

3 features of transmitters

Answer 2

1. presence in presynaptic neuron
2. calcium dependent release when presynaptic neuron depolarizes
3. specific receptors for the substance must be present on the postsynaptic cell

Question 3

dale’s principle

Answer 3

thought that one nerve was only responsible for releasing one neurotransmitter
proven wrong

Question 4

3 basic groups of neurotransmitters

Answer 4

“classic” low-molecular weight
gases
neuropeptides

Question 5

life cycle of neurotransmitter

Answer 5

1. synthesis
2. storage
3. release
4. postsynaptic effects
5. inactivation

Question 6

classic low-molecular weight/small-molecule transmitters

Answer 6

synthesized in axon terminals, packaged in small vesicles, and stored there until release

Question 7

gases

Answer 7

synthesized in nerve terminals
cannot be stored in cells
highly lipid and water soluble

Question 8

neuropeptides

Answer 8

synthesized in soma
processed and packaged in large dense-core vesicles in the Golgi
transported to axon terminal

Question 9

steps of transmitter release

Answer 9

presynaptic depolarization -> Ca2+ entry -> transmitter release
- vesicles fuse with plasma membrane and release contents into synaptic cleft via exocytosis

Question 10

ionotropic

Answer 10

direct

Question 11

metabotropic

Answer 11

indirect

Question 12

3 mechanisms of inactivation of neurotransmission

Answer 12

1. diffusion
2. degradation
3. reuptake (into glia, or nerve terminals), not for neuropeptides

Question 13

acetylcholine

Answer 13

• most comes from septal nuclei and basal forebrain
• important for learning, memory, and other cognitive processes (attention and decision making)
• evolved defense that targets Ach transmission

Question 14

ach agonist

Answer 14

nicotine
- highly reinforcing, calming, increases concentration

Question 15

ach antagonist

Answer 15

scopolamine
- muscarinic antagonist, prevents the ability of medial temporal lobe structures to encode memory

Question 16

acetylcholinesterase/cholinesterase

Answer 16

enzyme that breaks down ach

Question 17

alzheimer’s disease

Answer 17

one cause is a reduction of cholinergic neurons in the midbrain, leading to reduced availability of ach in the mediation of memory processes
also characterized by accumulation of neurofibrillary tangles or extracellular plaques that are insoluble and block the projection of cholinergic projections

Question 18

structure of metabotropic receptors

Answer 18

have similar transmembrane structure as ionotropic receptors but lack pores to conduct ions
instead ligand binding triggers intracellular signaling via g-proteins

Question 19

areas of the brain more involved with neurotransmission

Answer 19

mostly in striatum and frontal cortex

Question 20

tracing of neurotransmitters

Answer 20

• neurons using a specific transmitter can be identified by the presence of the transmitter itself, or tagging proteins involved in any step of its life cycle
• mapping by immunohistochemistry and fluorescence probe-tagging, then imaging with electron microscopy
• radio-labeled probes (autoradiography) following in situ hybridization with antisense oligonucleotides for certain receptor subunits

Question 21

critical excitatory and inhibitory transmitters

Answer 21

• gamma-aminobutyric acid (GABA)
• glycine
• glutamate

Question 22

glutamate

Answer 22

• primary excitatory transmitter in the brain
• synthesis: mostly derived from glutamine taken into the presynaptic terminal
• storage: vesicular glutamate transporters (VGLUT) load glu into synaptic vesicles
• inactivation: clearance from synaptic cleft by reuptake proteins (GLAST, EAAT, GLT-1, mostly into glial cells)

Question 23

ionotropic glutamate receptors

Answer 23

NMDA, AMPA, kainate

Question 24

metabotropic glutamate receptors

Answer 24

8 members in 3 classes

Question 25

gamma-aminobutyric acid (GABA)

Answer 25

- primary inhibitory transmitter - synthesis: from glutamate via glutamic acid decarboxylase with pyridoxal phosphates as a co-factor - storage: transporters bring into synaptic vesicles - release: at inhibitory synapses, many are interneurons, but the primary projection neurons in the cerebellum and striatum use GABA - inactivation: high-affinity transporters in presynaptic terminals and glia

Question 26

biogenic amines (monoamines)

Answer 26

regulate many brain functions and are also active in the pns involved in mood and affect motivation, attention, and arousal neurons releasing them are typically localized into small groups in the brainstem

Question 27

catecholamines

Answer 27

made of a catechol and amine - epinephrine, norepinephrine, dopamine - synthesis: in presynaptic terminals (enzymes arrive via axonal transport, precursors are generally taken up directly by presynaptic terminals) - storage: usually small clear vesicles - release: calcium dependent vesicle fusion - receptors: metabotropic - inactivation: enzymatic degradation and re-uptake transporters

Question 28

dopamine

Answer 28

dopamine neurons are localized in the brainstem structures substantia nigra and ventral tegmental area

Question 29

dopamine neurons respond to

Answer 29

1. unexpected delivery of reward 2. cues that precede rewards 3. pause when expected rewards do not occur - reward prediction error

Question 30

norepinephrine

Answer 30

involved in wakefulness, attention and feeding behaviors localized in the midbrain and send widespread and diffuse projections to much of the rest of the brain respond to alerting stimuli

Question 31

epinephrine

Answer 31

localized in brainstem/midbrain/thalamus

Question 32

5-hydoxytryptamine (5-HT)/serotonin

Answer 32

involved in sleep, wakefulness and mood localized in the pons and upper brainstem, widespread functions to the forebrain - synthesis: 2 step process starting with tryptophan in the brainstem - storage: vesicles - inactivation: uptake by specific serotonin transporter - receptors: one ionotropic, multiple metabotropic, target of hallucinogens such as LSD

Question 33

antagonists of ATP

Answer 33

caffeine theophylline

Question 34

5 categories of peptide neurotransmitters

Answer 34

- brain-gut peptides (substance P: pain) - opioid (enkepahlin, endorphins: analgesia, euphoria) - pituitary (vasopressin, oxytocin: bonding, lactation) - hypothalamic (LH: sex) - miscellaneous (Neuropeptide Y: energy balance, eating)

Question 35

endocannabinoids

Answer 35

heavily expressed in striatum (motivation), substantia nigra (dopamine neurons), hippocampus (memory and spatial location), cerebellum (movement) - unconventional bc: postsynaptic release, non-vesicular, receptors are pre-synaptic