BIOL 461 Neurobiology Midterm

dorsal

up toward top of head

ventral

down toward base of head

rostral

toward front (nose)

caudal

toward back (occipital lobe)

medial

middle

lateral

away from middle

anterior

front

posterior

back

coronal plane

saggital plane

horizonatal plane

why use intracellular recording?

you need precise real time Vm, EPSP/IPSP

pros/cons of intracellular recording?

get the voltage, see sub-threshold events

one cell at a time, invasive, fragile seal no movement

why use extracellular recording?

to listen in on multiple nearby neurons while animal behaves

pros/cons of extracellular recording?

multiple cells, during behavior, more stable than intracellular

no sub-threshold events, artifact signals, spike shape depends on geometry between electrode and neuron

why use tetrodes/arrays?

you need more spikes or separation of neighbor cells

pros/cons of tetrodes/arrays?

many simultaneous neurons

invasive, depth trade offs

why use neuropixels?

want big and dense recordings across structures

pros/cons of neuropixels?

orders of magnitude scale, large datasets

lots of data but less than 1% of brain, analysis bottleneck

why use spike raster plots?

see link between firing and stimulus

pros/cons of spike raster plots?

good population timing view

hides sub-threshold events, needs sorting and alignment

why use patch clamp?

prove channel function or kinetics

pros/cons of patch clamp?

single protein precision, clear mechanism

cannot collect much data at once, specific preparation

why use calcium imaging?

need large field of view, cell type targeting, movie of many neurons

pros/cons of calcium imaging?

big field, genetic targets, record during behavior

measuring Ca and not voltage directly, Ca slower than AP deconvolve

why use protein calcium sensor?

cell type specificity, chronic imaging

pros/cons of protein calcium sensor?

targeted, stable, multi-color

needs viral or transgenic delivery

why use voltage imaging?

want fast voltage events and optical readout

pros/cons of voltage imaging?

direct measure, higher fidelity than calcium imaging

less mature, finicky

why use optogenetics?

want to activate cells

pros/cons of optogenetics?

high temporal and spatial resolution, animals can behave during

viral and transgenic delivery is hard

why use MRI?

need anatomy

pros/cons of MRI?

whole-brain volume, non-invasive

does not show neural activity

why use fMRI?

want to map whole brain while it is engaged

pros/cons of fMRI?

non-invasive, see deep structures

slow, subject must lay still, variation in interpretation

why use MEG?

need good temporal resolution without a magnet

pros/cons of MEG?

faster than fMRI, non-invasive

weaker signal, less depth than fMRI 

why use EEG?

want to measure while person does moving tasks, cheap

pros/cons of EEG?

good temporal resolution, portable

artifacts, poor spatial resolution, averaging of signals

cerebrum

thought, memory, voluntary movement, sensory perception and made up of frontal, parietal, temporal, occipital lobe

corpus callosum

connects left and right cerebral hemispheres to communicate

cerebellum

balance, movement, posture

brain stem

breathing, heart rate, blood pressure, sleep-wake cycles

spinal cord

transmits messages between brain and body

gray matter

neuron cell bodies, dendrites, synapses

white matter

myelinated axons

neural inhibition

any process that reduces a neurons chance of firing action potentials

cocaine

-natural coca plant

-agonist

-blocks dopamine reuptake via DAT

-targets dopamine (pleasure) and noradrenaline (readiness) system

-increases synaptic dopamine, euphoria

amphetamine

-synthetic
-false substrate/releaser

-releases dopamine instead of reuptake
-targets dopamine (pleasure), noradrenaline (readiness), serotenergic system
-increase synaptic dopamine and serotonin, alertness

caffeine

-natural coffee bean

-antagonist
-blocks A1/A2A receptor from binding adenosine to calm

-targets adenosine, dopamine, noradrenaline systems

-prevents neural inhibition, alertness

THC

-natural cannabis plant

-partial agonist

-activates CB1 GPCR which leads to decreased GABA and glutamate release

-targets endocannabinoid, perception, neural activity systems

-relaxation, altered time sense, mild euphoria

LSD

-semi-synthetic from fungus

-agonist

-activates 5-HT2A metabotropic receptor

-targets serotinergic system

-hallucination, sensory perception altered

PCP

-synthetic

-antagonist

-blocks NMDA ionotropic receptor

-glutamate, dopamine, perception, neural activity systems

-dissociation, psychosis, hallucination

psilocybin

-natural mushrooms

-agonist

-activates 5-HT2A receptor

-targets serotinergic system

-hallucination, sensory cross talk

morphine

-natural opium poppy

-agonist

-activates u-opiod GPCR

-targets opiod, dopamine, neural activity systems

-sedation, pain relief, euphoria

heroin

-semi-synthetic from morphine

-agonist

-converts to morphine and binds to u-opiod GPCR’s that block GABA neurons 

-euphoria, highly addictive

nicotine

-natural tobacco

-agonist

-activates ACh ionotropic receptor

-targets dopamine and noradrenaline systems

-increased dopamine release

-stimulation and mild dependency

alcohol

-natural fermentation

-depressant

-enhance GABA-A by blocking NMDA receptor and fluidizing membrane

-targets dopamine and neural activity systems

-sedation, motor impairment

aspirin

-semi-synthetic willow bark

-enzyme inhibitor

-inhibit COX enzymes which blocks prostaglandin synthesis

-targets peripheral prostaglandin system

-pain relief, anti-inflammatory

naloxone

-synthetic

-antagonist

-competes u-opiod receptor without activating it

-reverses opiod overdose

MDMA

-synthetic

-false substrate/releaser

-blocks serotinergic system

-targets dopamine, perception, serotinergic system

-euphoria, neurotoxic at high dosage

acetylcholine (ACh) ionotropic

ionotropic nicotinic ACh receptor allows Na+ in and K+ out

neuromuscular junction, depolarizes cell for muscle contraction

acetylcholine (ACh) metabotropic

metabotropic muscarinic ACh GPCR receptor opens resting K+ channels

vagus nerve in heart, hyperpolarizes cell to slow heart rate

GABA (mature)

ionotropic GABA-A receptor permeable to Cl-

hyperpolarizes cell to inhibit action potentials

GABA (developing)

ionotropic GABA-A receptor permeable to Cl-

depolarizes cell to excite action potentials by increasing intracellular Cl- (to flow out)

glycine

ionotropic glycine receptor permeable to Cl-

hyperpolarizes cell to inhibit action potentials in the spinal cord

glutamate AMPA

ionotropic AMPA receptor allows Na+ in and K+ out to quickly depolarize cell for EPSPs

glutamate NMDA

ionotropic NMDA receptor permeable to Na+, K+, Ca2+ to depolarize cell and allow Ca2+ entry

adrenaline (epinepherine)

metabotropic beta-adregenic GPCR receptor turns on cAMP—>PKA—>Ca2+ to allow more Ca2+ entry to increase heart rate and strengthen contraction

what 2 things does an NMDA receptor need to open?

1) glutamate binds to NMDA receptor
2) post-synaptic membrane must be depolarized to remove the Mg2+ ion blocking NMDA receptor at rest

what happens once the NMDA receptor is open for binding?

Ca2+ influx triggers LTP (stronger synapses) and more AMPA receptors are inserted into postsynaptic membrane for more EPSPs

associative learning

when two neurons are regularly active at the same time, their communication becomes stronger

AMPA vs NMDA receptors

AMPA: only needs glutamate binding, fast, initial cell depolarization

NMDA: glutamate binding AND Mg2+ block removal, slow, LTP

what neurotransmitter does curare (paralysis) block?

ACh via nicotinic ACh receptor

what neurotransmitter does acetylcholinesterase block?

ACh via degrading ACh in synaptic cleft

what neurotransmitter does atropine block?

ACh via muscarinic ACh receptor

what drugs effect mature GABA?

barbituates
muscimol
benzodiazepines
picrotoxin (blocks Cl- channel)

what neurotransmitter does picrotoxin block?

mature GABA

what neurotransmitter does strychnine block?

glycine receptor in spinal cord/brainstem

what does length constant 𝜆 represent?

how far a potential spreads before dropping to 37% of initial amplitude

larger 𝜆 = further spread

𝜆 is proportional to radius, bigger axonal radius = further spread

what is the quantal hypothesis?

each vesicle unit releases as an integer multiple

what are v-SNARE (vesicle docked) and t-SNARE (presynaptic membrane docked) proteins?

upon Ca2+ binding in presynaptic membrane, they twist together to fuse vesicles to membrane

what is botulinum toxin?

cleaves SNARE blocking ACh NT release thus muscles cannot contract called flaccid paralysis (botox)

what is tetanus toxin?

targets SNARES in inhibitory spinal neurons blocking GABA and glycine release thus cell uncontrollably excites and rigid paralysis (lockjaw)

what do experiments conclude about the role of Ca2+ in synaptic transmission?

1) removing extracellular Ca2+ stops NT release even w/ AP
2) increasing intracellular Ca2+ invokes NT release w/o AP
3) EPSPs occur in integer mulitples

what are mEPPs? (mini endplate potentials)

tiny postsynaptic depolarizations that occur spontaneously without stimulation in low Ca2+ environment

what is tetrodotoxin (TTX)?

drug that blocks voltage-gated Na+ channels to kill AP (fatal)

what is myelin?

fatty sheath that wraps around neuronal axons to speed AP

time constant 𝜏 (𝜏=RC)

sets how fast membrane voltage changes after a current

smaller 𝜏 = faster voltage response

2 criteria for ion to cross PM?

1) open channel/transporter
2) electrochemical gradient driving force

what is Eion?

balance when chemical and electric gradient cancel

mamallian E values (K+, Na+, Cl-, Ca2+)

Ek+= -80 mV
Ena+= +60 mV
Ecl-= -65 mV
Eca2+= +120 to +130 mV

what happens when Vm=Eion (reversal potential)

no net flux of ions

ionotropic receptor

neurotransmitter gated ion channels
faster than metabotropic

metabotropic receptor

GPCRs activated by neurotransmitter binding
slower than ionotropic
amplifies signals

long-lasting effects

reinforcement

what you EXPECT versus what actually HAPPENS

drugs hijack brains natural reinforcement learned by altering dopamine reward prediction error signal

e.g. cocaine use leads brain to interpret taking drug as a positive prediction error (good surprise)

reward system

-dopamine rich areas

-VTA, NAc, medial forebrain
-direct stimulation is VERY pleasurable

serotonergic system

-raphe nuclei
-neurons project every way, reason why ser target drugs affect mood everywhere

glutamate/GABA system

-balance excitation/inhibition
-suppress dopamine to reduce APs