Neuroscience of Motivation Midterm 1

What is the basis of motivation and what exemplifies this?

There is a NEUROBIOLOGICAL BASIS of motivation, and ELECTRICAL SELF-STIMULATION exemplifies this

• electrical stimulation as a reward that leads to behaviour

What is MOTIVATION?

MOTIVATION is a modulatory and coordinating influence on the direction, vigor, and composition of behaviour

• this INFLUENCE comes from internal (Motivational state), external (Incentive Stimuli), and social levels of behaviour and neural organization

What is a MOTIVATIONAL STATE?

A MOTIVATIONAL STATE is internal conditions responsible for a common influence on behaviour reflecting the integration of diverse factors

What is INCENTIVE STIMULI?

INCENTIVE STIMULI are external sensory inputs that promote behaviour

• including natural goal objects like food

What were the 3 MOTIVATIONAL CONCEPTS in the story of the male and female rat in a shared borough?

From the story of the female and male rat who share a borough:

The reproductive behaviour of rats illustrates MOTIVATIONAL INFLUENCE → where changes in hormonal status + experience alter 1. Evaluation and selection of goal objects 2. the impact of external stimuli 3. vigour of goal-directed behaviour 4. and prepotency of sensorimotor units of action

1. THERE IS COMPETITION BETWEEN MOTIVATIONAL STATES (ACTIVE SELECTION of a rat’s thirst and sex motivations)

2. INCENTIVE STIMULI SHAPE COMPETITION (sensory experience of mate vs water consumption, which is better?)

3. THERE ARE NEUROBIOLOGICAL DETERMINANTS OF STATES (ex. changes in gonadal hormones leading to receptivity)

What was Richter’s DRIVE REDUCTION VIEW? (focus and problems)

RICHTER held a DRIVE REDUCTION VIEW, also known as HULL’S DRIVE THEORY, whereby drives are agitations that compel you to reduce internal physiological tension from BIOlOGICAL NNEEDS, to improve survival

• RICHTER interpreted all activities to be direct or indirect attempts at drive reduction

• reduction activities are strengthened + necessary for learning to occur

HE FOCUSED ON irritability, organ contractions, isolating and administering biological extracts (hormones), but where were they acting?

PROBLEMS: variability in organ periodicity, rats develop periodicity, the same “DRIVE” can create variable behaviours, organ removal does not affect behaviours (one ovary, thyroid, parathyroid, pituitary, adrenal)

Why is MEASUREMENT critical to studying motivation?

As there are many different types of behaviours, measurement (balloons for stomach contractions, tubes for added inconvenience, etc.) is central in capturing ISOLATION

• isolation is a caveat of experimental work, as in nature there are multiple competing behaviours and DRIVES

What are the tradeoffs of experimental controls + what was the assumption paired with these tradeoffs? What is 1 PROBLEM IN PRECLINICAL RESEARCH?

EXPERIMENTAL CONTROL has trade-offs of having rats in CONSTANT LIGHT + DEVOID OF EXTERNAL STIMULI

• under normal conditions, we expect movement from rats, but under experimental conditions there is STILL SPONTANEOUS ACTIVITY … therefore RICHTER + OTHERS believed MOTIVATION must therefore be derived from within the organism!

A PROBLEM IN PRECLINICAL RESEARCH is the underuse of female subjects (Sex as a biological variable)

Gross body movement in rats is PERIODIC, why was this a window to studying motivation? What type of studies did this lead to?

RICHTER found that diffuse gross body activity occurs rhythmically

• this generated questions of HOW periodicity was produced and WHICH organ it came from?

Researchers predicted movement may be driven by organ systems, such as THE STOMACH and CONTRACTIONS motivating the search for food sources as the utility of movement!!!!!

• “The inference, therefore, is quite logical … 2 hours periods of gross bodily activity in the rat are associated with periods of gastric movement + are related to hunger responses of the animal.”

What were 3 details about GASTRIC RHYTHM MOTIVATION studies?

1. There was a similar periodicity between animals and humans for stomach contractions (~2 hours)

2. RICHTER believed that hunger promotes movement through the search for food

3. Gross body movement AND stomach contractions were unable to be measured at the same time (lots of experimental issues)

What were the 5 research attempts at measuring both stomach contractions and gross body movement? What were the problems with each method?

RESEARCHERS were unable to put balloons in rat’s stomaches, as rats bit holes through the tube or were asphyxiated from small throats

1. BULLFROGS did not move for many days

2. PIGEONS had a 30 minute average rate of activity + kept expelling the balloon

3. HUMAN BABIES had a periodic activity average of 45 minutes + cardiac sphincter spasms

4. ADULT MEDICAL STUDENTS had stomach contractions that SUCCESSFULLY coincided with movements during sleep → this confirmed RICHTER TO HIMSELF AND OTHER DRIVE-REDUCTIONISTS

What was the IMPROVED FOOD-HABIT MEASUREMENT of RICHTER? What did this prompt RICHTER to think about on HOW activity becomes associated with eating?

RICHTER’s improved food-habit measurement included custom chambers with a feeding compartment that rats must enter!!! The tunnel leading to the food-box was built to be inconvenient to discourage non-hunger related entrance.

• RICHTER believed hunger contractions stimulated the organism to activity, but HOW does activity become associated with EATING PROCESS?

PERIODICITY DEVELOPMENT IN PUPS THROUGH CONTINUOUS MOVEMENT

How does PERIODICITY develop in pups through CONTINUOUS MOVEMENT?

PUPS (baby rats) must learn that the hunger drive can only be satisfied by consuming food (milk)

• CONTINUOUS, UNDIRECTED MOVEMENT is not directed, but permits the pup to discover mother’s tit

A reduction in the hunger drive occurs during milk consumption and refines this behaviour

What are 3 PROBLEMS with RICHTER’S DRIVE-REDUCTION VIEW OF MOTIVATION? How does he counter these in POST-HOC?

3 PROBLEMS WTIH DRIVE-REDUCTION:

1. MOVEMENT is not periodic in all animals (rats have to develop periodicity whereas some animals have rhythmic movement from birth)

2. MOVEMENT varies for other reasons (ex. oestreous cycle running)

3. ANIMALS ALSO RUN FOR SEEMINGLY NO REASON AT ALL

RICHTER creates a POST-HOC EXPLANATION to defend his DRIVE-REDUCTION HYPOTHESIS: that hunger arises from stomach contractions, which motivates animals to move and search for food

• THOUGH RAT JELLY BEAN PUPS move continuously before ever knowing that food quells hunger

• RICHTER claims that RAT PUPS develop slower than other animals (bunnies + guinea pigs) therefore other types of pups have periodic stomach contractions, JUST NOT RAT PUPS

What are 4 FINDINGS from studies looking at female spontaneous running activity and 2 IMPLICATIONS?

1. Vaginal smears - cornified epithelial cells during oestrous period every 4 days → FEMALE OESTROUS CYCLE IS 4 DAYS

2. FEMALE RATS have a regular 4-day cycle where they run a LOT then on only a fraction of that on other 3 days, coinciding with cycle

• this 4-day cycle is absent in pregnancy and lactation

3. OVARIES must be in-tact to see periodicity

4. Hormone removed from the pig ovaries increased running

RICHTER BELIEVES increased motility during heat is to attract males… can rats run for other reasons?

THIS BEGGED THE QUESTION “WHERE DOES THE HORMONE ACT?” if there is a different periodicity than stomach contractions and different mechanism (uterus removal)

“we are inclined to hold that the secretion, then, must take effect in the central nervous system” FiNALLY TALKING ABOUT BRAIN

What are 3 FINDINGS from studies looking at male spontaneous running activity and 1 implication?

MALE RATS do not have 4-day cycles

1. The removal of the seminal vesicles (CASTRATION) has no effect on motility

2. The motility of male rats is sensitive to OVARIAN extracts (estrogen) binding to receptors + possibly promoting dopamine production, increasing movement

INCONSISTENT varying reproduction motivation than hunger, lots of plot holes in DRIVE-REDUCTION THEORY OF MOTIVATION

How is reproduction different than other drives?

REPRODUCTION poses no immediate harm like hunger and is different among female rats (oestrous 4-day cycle relying on in-tact ovaries) and male rats (unaffected by castration and sensitive to ovarian hormone estrogen - binding in place of male hormones and producing increased movement)

What behaviours are periodic besides hunger and sex? What are 2 ways this threatens DRIVE-REDUCTION VIEW and RICHTER’s solution?

There are multiple behaviours with VARYING periodicity: DRINKING,

URINATION, DEFECATION

• RICHTER ties this all to the affected organs, BUT once organs are removed, there are no effects on movement: one ovary, thyroid, parathyroid, pituitary, adrenal

• There are also other sophisticated behaviours beyond drive-reduction that animals produce - burrowing, gnawing, nest building, etc.

• RICHTER now tries to shift focus on ISOLATING these behaviours (nest building) through THERMOREGULATION which is artificial and not found in nature

How does RICHTER use thermoregulation to support DRIVE-REDUCTION VIEW? What problems arise as RICHTER studies thermoregulation?

1. RICHTER holds that THERMOREGULATION is the unifying factor of various nest building behaviours through HEAT CONSERVATION and INCREASED HEAT PRODUCTION

2. He states that FAT CONSERVATION and HAIR GROWTH quell the same need

3. COPIOUS AMOUNTS of variable behaviour are revealed … WHY are there so many types of behaviour to satisfy the same NEED?

• in nature, thought there is no BIOLOGICAL NEED to do so, rats will run on wheels despite wasting potential energy that would otherwise be used for gathering food

What is SIGN-TRACKING?

IN SIGN-TRACKING RATS (STs) they approach, chew, sniff, and engage with a lever or light cue (Conditioned Stimulus) as if it were a reward (unconditioned stimulus)

• INDIVIDUAL differences between rat responses causes more issues for RICHTER’s DRIVE-REDUCTION

What is GOAL-TRACKING?

IN GOAL-TRACKING RATS (GTs) they ignore the physical lever or light cue and immediately approach the location where a reward is delivered (nose poking) upon the presentation of a cue

• INDIVIDUAL differences between rat responses causes more issues for RICHTER’S DRIVE REDUCTION

What is the CONTRAFREELOADING EFFECT and why does this challenge the DRIVE-REDUCTION VIEW?

THE CONTRAFREELOADING EFFECT is when animals are given freely available food or work to receive the same food, they will prefer to work

• expensive energy wise, not adhering to DRIVE-REDUCTION VIEW of need satisfaction improving SURVIVAL

• pet cats and dogs do not show this effect

What is SENSATION SEEKING and why does this challenge DRIVE-REDUCTION VIEW?

EVEN when there is no biological need, as in the case of turning on a light…

• rats will press a lever despite no relationship with a biological need

Sign tracking and Goal tracking (INCENTIVE MOTIVATIONAL VIEW) may be a way to answer this, why would an animal engage in a behaviour that has no biological need?

What does ADRENALECTOMY reveal about motivation?

ADRENALECTOMIZED RATS tell us about THE VOLITIONAL ADDRESSING OF NEEDS, as they have an increased salt appetite

• animals move for all sorts of reasons, but can they direct this movement to VOLITIONALLY satisfy an IMPOSED survival need?

RICHTER observed that the failure for pre-surgery rats to differentiate between salt solution and tap water is because…

• salt solution is too weak

• or their salt appetite is LESS SENSITIVE as a result of their needs being met

He sees all of these behaviours as either direct or indirect attempts at drive-reduction and that INCREASED SALT APPETITE is specIfic for a loss of adrenal grand secretions (hormones)

What are the 4 components of BINDRA’S INCENTIVE MOTIVATIONAL VIEW?

INCENTIVE MOTIVATIONAL VIEW is that behaviour is being “pulled” from external rewards and reinforcements/environemnt, rather than being “pushed” from internal biological needs

1. Here, a CENTRAL MOTIVATIONAL STATE (CMS) - promoting eating, copulation, attack, or avoidance - is a temporary state that is determined by internal organismic conditions (hormones, sickness, etc.) and the environmental stimulation from external INCENTIVE STIMULI (odour of food, sight of a sexual object, etc.)

2. CENTRAL MOTIVE STATE is created by both specific state factors (hormonal levels, sickness, etc.) and specfic types od

3. CHOICE OF ACTION (approach or withdrawal) is determined by nature of INCENTIVE OBJECT in the situation

4. Response in a situation is a FRESH CONSTRUCTION, each time it occurs, created by a momentary CMS and the environmental arrangement of the incentive stimuli each time

INCENTIVE STIMULI can be unconditioned (food, sex, water) or conditioned incentive stimuli (notification, money, etc.)

How is measuring INDIVIDUAL DIFFERENCES problematic for DRIVE-REDUCTION VIEW? What are possible explanations for these differences?

Measuring INDIVIDUAL DIFFERENCES is problematic for DRIVE REDUCTION VIEW, because though animals may have the same drive state, their behaviours are so different:

GOAL TRACKERS see levers as Pavlovian unconditioned stimuli

SIGN TRACKERS see levers as a Pavlovian conditioned stimuli → ALSO CALLED AUTO SHAPING where animals shape their own behaviour despite no actual affect on whether they get food or not

• sign trackers may desire the presentation of the lever, through an associative process where it can reduce hunger ???

How can CHEMOGENETICS and DEVALUATION be used as a possible explanation for the differentiation between GOAL TRACKERS and SIGN TRACKERS?

It is thought that a connection between the NUCLEUS ACCUMBENS (NA) and BASAL LATERAL AMYGDALA (BLA) is important for sign tracking and goal tracking → relating to the capacity for motivational states to respond to incentive stimuli, are animals sign tracking because they are hungry?

hM4Di is a chemognetic receptor that is mutated

• through virus injection, both NA and BLA express mutated inhibitory chemogenetic (i inhibitory and q excitatory) g-coupled receptors where common ligand, Clozapine-n-oxide (CNO) can bind

• normally: STs are not affected by food devaluation, GTs are affected by food devaluation (satiety)

• in studies with NA-BLA DISCONNECTION + FEEDING RATS → SIGN TRACKERS become sensitive/affected to devaluation (less lever interaction if devalued) GOAL TRACKERS become less sensitive to devaluation (still interacting with location of food)

What are 3 problems with the methods of CHEMOGENETICS in disconnecting the Nucleus Accumbens and Basal Lateral Amygdala?

1. DISCONNECTING the Nucleus Accumbens and the Basal Lateral Amygdala tells us nothing about NEUROTRANSMITTERS

• as NA is majority GABAergic neuron site, the interactions between inhibition and excitation from NEUROTRANSMITTERS may have had an impact on sign and goal tracking

• but now disconnected

2. The Nucleus Accumbens and the BasoLateral Amygdala are very far, the disconnection between them is very LARGE and affects multiple regions

3. When initiating chemogenetic disconnection, we MUST EACH DISCONNECTION on ONE SIDE only of the brain, leaving the other side of these bilateral structures unaffected

• one side with normal BLA

• other side with normal NA

What is VOLTAMMETRY? What does it tell us about Sign Tracking and Goal Tracking? What’s an important caveat about VOLTAMMETRY?

VOLTAMMETRY is an electromechanical technique to measure dopamine catecholemines, where a carbon fiber electrode in the brain senses when dopamine undergoes redox reaction to release electrons

• SIGN TRACKERS show elevations in dopamine release during the CS (sign) and decreases during the US (goal) → In Nucleus Accumbens

• Goal-trackers show relatively stable dopamine responses → in Nucleus Accumbens

IMPORTANTLY: Sign and Goal tracking dopamine responses are not related to movement - uncorrelated to their locomotor score + sign and goal trackers have a similar movement level before lever presentation

What are 3 reasons animals SIGN-TRACK?

1. Movement, hunger, operant conditioning

2. Stimulus Substitution poses that CS substitutes US

• lever substitutes for food

thirsty rats would bite a lever if they’re hungry

3. Conditioned Release poses that the state of the animal determines the response, lever holds the ability to release state specific behaviour

thirsty rats would lick a lever even when it normally predicts food

Summarize the 3 experimental studies looking at SIGN TRACKING through CS reinforcer type and depravation states!

EXPERIMENT 1 sign tracking trained with solid (biting) or liquid (licking) food

• Support for STIMULUS SUBSTITUTION as reinforcer identity plays a role in shaping sign-tracking behaviour

• Challenges STIMULUS SUBSTITUTION as animals trained with sugar liquid reinforcer did not lick when sign-tracking

EXPERIMENT 2 deprivation levels affect sign-tracking in water-deprived rats

• Problem for STIMULUS SUBSTITUTION as the stimulus is the same, but behaviours are different

• Problem for CONDITIONED RELEASE as the state (water deprivation) is the same, but behaviours are different

EXPERIMENT 3 sign-tracking is not a consequence of deprivation

• general arousal, movement, and bodyweight are all factors

What are the 3 main takeaways from the 3 experiments manipulating deprivation state and reinforcer type?

1. UNDER THE SAME MOTIVATIONAL STATE OF FOOD DEPRIVATION, nature of sign-tracking can be determined by reinforcer type (liquid vs solid)

2. LIQUID < SOLID REINFORCERS AT INDUCING CS CONTACT, but can be facilitated with more water deprivation (but still not as much as with food deprivation)

3. HIGH CS CONTACT using food are NOT PRODUCT OF REDUCED BODY WEIGHT FACILITATING CONTACT

More coherent with STIMULUS SUBSTITUTION, but can’t explain everything

• bust CONDITIONED RELEASE IN PLAINEST FORM is not working - hungry rats lick liquid US reinforcers when sign-tracking

How do we alter receptor expression using CHEMOGENETICS in 4 STEPS?

1. We need VIRUSES to deliver genetic information to cells

2. We need to control the content of this genetic information (receptor type—inhibitory or excitatory—and readability, are there lox sites?)

3. We then need enzymes to make genetic information readable

4. We need enzymes be expressed in specific cells in transgenic animals

What are the basic components of the COMPUTATIONAL MODEL of dopamine error signaling?

DOPAMINE is represented as error signal of predictions

1. UNEXPECTED REWARD (US) dopamine will peak at the presentation of the stimulus with a positive prediction error

2. EXPECTED REWARD (CS US Pairing) dopamine will peak at the presentation of CS and be stable when shown the US

3. UNEXPECTED OMISSION (CS no US) dopamine will peak at CS presentation and dip to a negative prediction error when missing the US expectation

V(t) is prediction at a given time

r(t) is reward

weird symbol is dopamine presence

How can current and frequency be altered in ELECTRICAL SELF-STIMULATION? How do rats react to it? What is a CURRENT? What is FREQUENCY?

LOW CURRENTS (smaller electrical gradient, electricity traveling smaller distances from the electrode) injected FAST and HIGH CURRENTS (electricity traveling greater distances from the electrode) injected SLOW produce the same amount of behaviour in rats

• Inserting an ELECTRODE into a rat’s brain at any location (NON SPECIFIC) will illicit volitional pressing of a lever to deliver electrical self stimulation that is NON SPECIFIC

• Currents: how great or small the distance of electricity travels from the electrode

• Frequency: How fast we deliver the current (HZ) per second

Same reaction if we stimulate a small area very fast or a large area very slow!!!

How can ELECTRICAL SELF STIMULATION AND SUGAR be used to show that artificial and natural stimulation of the brain are equated as a common currency?