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What is learning?
an enduring change in behavior as a result of experience
encoded by changes in the brain
What are the two types of learning?
non-associative and associative
What is non-associative learning?
When a stimulus is not paired with a behavior
What are two types of non-associative learning?
habituation
sensitization
What is associative learning?
when a response becomes associated with a stimulus
What are the two types of associative learning?
classical conditioning
operant conditioning
What is habituation?
decreased response to the same, repeated stimulus
tends to be toward non-threatening stimulus
what is sensitization?
Increased response to the same, repeated stimulus
tends to be toward a threatening or arousing stimulus
What is an animal commonly used to test habituation and sensitization?
Aplysia california and their Gill-Withdrawl Reflex
What is classical conditioning?
AKA Pavlovian conditioning
Learned response (CR) to a neutral stimulus by pairing the neutral stimulus (CS) with one (US) that evokes a natural response (UR)
What is associative learning?
Operant conditioning
Consequences of an action will determine how likely it is to happen again
Behaviors that lead to good outcomes will be repeated
Behaviors that lead to negative outcomes are less likely to occur again
Use of reinforcement or punishment to shape behavior
positive
negative
What is an example of positive reinforcement?
add appetitive stimulus following correct behavior
What is an example of negative reinforcement?
remove noxious stimulus following correct behavior
What is an example of positive punishment?
add noxious stimulus following behavior
What is an example of negative punishment?
remove appetitive stimulus following behavior
What is memory?
Internal records of past experience as a result of learning
What is short term memory?
Working memory: short term, active storage
What are the two types of long-term memory?
Declarative and non-declarative
What is declarative memory?
memories that can be recalled
semantic: facts or events that did not happen to you;
episodic: things that happened to you
What is non-declarative memory?
procedural: remembering how to do things like ride a bike
What type of memory does the hippocampus store?
declarative memory
episodic memory
semantic memory
What type of memory does the prefrontal cortex store?
working memory
What type of memory does the cerebral cortex store?
perceptual memory, semantic memory, priming
What type of memory does the amygdala store?
emotional memory
What procedure was performed on patient H.M.?
had 2/3 of his hippocampus removed at age 27
What were the effects of patient H.M.’s procedure?
he still had working memory and procedural memory
he could not convert new declarative memories into long term memories
he could not remember the years just before surgery
What were H.M.’s deficits?
anterograde amnesia and some retrograde amnesia
What did H.M.’s deficits tell us?
Memory has many facets, each facet does not necessarily rely on the hippocampus.
The hippocampus may be involved in converting/storing new memories into long term storage, but likely doesn’t store memories long term
What is the pathway for memory consolidation in the hippocampus?
sensory cortices → dentate gyrus → CA3 → CA1 → association cortices
What stage in memory consolidation are the sensory cortices active?
sensory information
What stage in memory consolidation are the dentate gyrus, CA3, CA1 active?
short-term memory
What stage in memory consolidation are the association cortices active?
long-term memory
What part of the brain are place cells located?
in the hippocampus
What are place cells?
networks of cells that fire when rat is in a specific place in the environment
silent when they are anywhere else
Where does long-term potentiation occur?
occurs in the hippocampus and amygdala
what is long-term potentiation?
persistent strengthening of synapses based on recent patterns of activity
What are ways to test memory?
radial arm maze
delayed t-maze
barnes maze
delayed matching to position (DMTP)
morris water maze
What does the radial arm maze test?
working and reference memory
What is the resting membrane potential in mV?
-60 and -80 mV
What 3 ions contribute to the resting membrane potential?
Sodium (Na+), Potassium (K+), Chloride (Cl-)
How does the neuron maintain resting membrane potential?
sodium-potassium pumps and potassium leak channels
Do sodium-potassium pumps or potassium leak channels use ATP?
sodium-potassium pumps
what are the properties of ion channels (Na+ and K+)
voltage-gated
use passive diffusion
no energy
ion channels only let molecules that are small enough to pass through
What are the characteristics of the resting potential?
Open passive K+ channel
creates the resting potential
Closed gated K+ channel
Closed Na+ channel
What are the characteristics of depolarization to the threshold?
Open passive K+ channels
Open Na+ channel
some Na+ channels open, depolarizing cell to threshold
Closed gated K+ channel
What are the characteristics of depolarizing after threshold?
Open passive K+ channels
Na+ channels are inactivated
Gated K+ channels open
re-polarizing and even hyper polarizing the cell (after potential)
What are characteristics of returning to resting potential
all gated channels close
the cell return to its resting potential
What are the two types of refractory periods?
Relative and absolute
What is absolute refractory?
Another action potential cannot occur
v-gated Na+ channels inactivated
What is relative refractory?
Another action potential can occur if a super strong stimulus is present
V-gated K+ channels open
What are two ways to improve conduction in a neuron?
increase myelination and increase diameter of axon
What sensation does the primary sensory neuron, Aα, perceive?
proprioception
What sensation does the primary sensory neuron, Aβ, perceive?
touch
What sensation does the primary sensory neuron, Aδ, perceive?
pain (mechanical and thermal)
What sensation does the primary sensory neuron, C, perceive?
pain (mechanical, thermal, chemical)
What are the characteristics of EPSP?
Small depolarization (+) of the membrane
Brings the neuron a bit close to threshold → more likely to fire action potential
Excitatory neurotransmitter action
glutamate
What are the characteristics of IPSP?
Small hyperpolarization (-) of the membrane
Bring neuron farther away from threshold → less likely to fire action potential
inhibitory neurotransmitter action
Gaba
What is summation?
when EPSPs and IPSPs add together
What are glutamate receptors?
NMDA, AMPA, mGluR
What happens when glutamate binds to glutamate receptors?
allows cations (Na+ and Ca2+) to enter cell
What happens when the presynaptic cells releases GABA and GABA binds to GABA receptors
Cl- channel opens, negative charge spreads throughout cell. This is IPSP
What happens when a positive action potential makes it to the axon terminal?
voltage gated calcium channels open. the calcium bind to vesicles causing them to reach neurotransmitters
what is synaptic plasticity?
change in strength (or number) of synaptic connections
how long is short term synaptic plasticity?
seconds, minutes
What presynaptic changes can happen in relation to synaptic plasticity?
Facilitation: increased NT release
Depression: decreased NT release
What specific presynpatic changes occur due to short term synaptic plasticity?
Number of release/docking sites
Ca2+ channel conductance
Amount of NT per vesicle
Number of vesicles = size of ready-releasable pool
How long is long term synaptic plasticity?
hours to days
What are the two types of long term synaptic plasticity?
Long-Term potentiation
increased EPSP after high frequency stimulation
AMPA receptors insertion
Long-Term depression
Decreased EPSP following low frequency stimulation
AMPA receptors internalization
What can we learn from in vivo electrophysiology?
Which cell populations fire during behavior
how certain cells are firing
frequency, temporal aspects
What can we learn from in vitro electrophysiology?
How ions are moving through the membrane
voltage clamp: holding the voltage constant to see how ions move
at a particular voltage, what ions are moving in and out of the cell
How certain ions moving through the membrane influence membrane voltage
current clamp: injecting a specified amount of a particular ion and seeing how it changes the voltage of a cell
can measure action potentials, and show which ions contribute to action potential firing
What are the long term effects of drinking?
substance use disorder
co-users were at 3/38 greater odds of having an AUD but not CUD
behavioral
decreased academic performance
SAM doubled the odds of drunk driving, social consequences, and harms to self
neuro-cognitive
poorer selective attention accuracy
greater discounting of future rewards
What is non-contingent exposure
experimenter-adminstered, animal does not choose to take the drug
intraperitoneal injection, subcutaneous injection, oral gavage
what does the animal model of drug self-administration
operant task: response required for reinforcement
routes: I'.V/, oral ingestion, inhalation
dose, reinforcement schedule, cues can all be manipulated
what this can tap into:
cumulative intake
patterns of intake
increase in intake (escalation)
motivation to receive the drug
what are self-administration caveats?
animals dont like many of the drugs humans do: THC and LSD
What happens in the brain when you consume alcohol and THC together?
both bind to cannabinoid receptor type 1 (CB1R)
located on membrane of presynaptic axon terminal
inhibit presynaptic neuron
increase or decrease neurotransmitter release
How does combined exposure to alcohol and THC affect the current frequency in a CB1R-dependent manner?
reduces miniature excitatory postsynaptic
In control rats, 40 Hz stimulation inhibits local field potential in prefrontal cortex
LFP: firing of a group of neurons; extracellular recording
CB1R agonist injection increased LFP2, i.e., reduced the magnitude of the initial inhibition
CB1R stimulation ___ PFC inhibition under 40 Hz
reduces
GABAaR stimulation ____ that inhibition
restores
What does GABA facilitate?
LTD
What are classical hormone receptors?
nuclear receptors
directly influence genetic expression
What are non-classical hormone receptors?
cell-surface receptors
indirectly influence genetic expression via second messengers
What are peptide hormones?
lipophobic
act through non-classical signaling
Ex. angiotensin, gherkin, insulin, leptin, oxytocin, somatostatin, vasopressin, growth hormone
What are different sex hormones?
estrogens
primary type: estradiol (E)
androgens
testosterone (T)
dihydrotestosterone
What is the HPG Axis: sex hormone signaling for males
luteinizing hormone (LH) stimulated T production in testes
follicle-stimulating hormone (FSH) and T promotes sperm production
What is the HPG Axis: sex hormones for females
follicle-stimulating hormone (FSH) stimulates E production in ovaries
lutenizing hormone (LH) stimulates P production - prepare for ovulation
What are the two major phases of the human menstrual cycle
follicular phase: before ovulation, egg is maturing, endometrium is being built up
luteal phase: after ovulation, egg is dying, endometrium reaches peak thickness
What are the coordination of hormones in the human menstrual cycle?
LH surge triggers ovulation
progesterone stimulates endometrial shedding
What issues can occur with the humans menstrual cycle?
endometrial cancer
polycystic ovary syndrome
infertility
What are the four phases of rat estrous cycle?
destroys 1
sometimes called metestrus
diestrus 2
proestrus
peak E and P
ovulation
sex behavior
estrus
sex behavior
How do you determine stages of the estrous cycle?
vaginal lavage
wash out vaginal cells, stain, visualize
cornification
terminal differentiation and programmed cell death
cells look different depending on the day of estrus cycle
diestrus: cells dies and leukocytes clear debris
proestrus: high E, healthy cells with nuclei
estrus: lower E and P, cornfield epithelial cells (dying)
What are the characteristics of the estrous cycle?
sex behavior is dependent on sex hormone levels
females are only receptive to copulation when estrogen and progesterone are high
What are the characteristics of the menstrual cycle?
humans and primates
sex behaviors is independent of sex hormones
females are receptive to copulation regardless of hormone levels
What are sexual behaviors of male rat?
mounts
intromission
ejaculation
What are sexual behaviors of female rats?
proceptive behaviors
hopping, darting, ear wiggling
lordosis
What brain regions are involved in sexual behavior in rats?
medial pre optic area
basolateral amygdala
mediobasal hypothalamus
How is the medial preoptic area involved in sexual behavior in rats?
in anterior hypothalamus
for masculine sexual behaviors, ex. mounting
lesions inhibit copulation
How is the basolateral amygdala involved in sexual behavior in rats?
lesions reduce rates of responding to receive a sexual reinforcer
used male rats as subjects
sexual activity is normally rewarding
How is the mediobasal hypothalamus involved in sexual behavior in rats?
for female rat sexual receptivity
What are the the two chemicals involved in sex behavior?
dopamine and opioids
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