Last chapters of brain and behavior

Learning

the process of acquiring new and relatively enduring information (Acquisition), involves changes in the brain as a result of experience

Memory

* The ability to store and retrieve information
* The specific information stored in the brain
* Research has revealed fundamentally different types of memory.

Amnesia: 

Loss of memory

Karl Lashley - Experimental Psychologist

* 1920’s – 1950’s
* Looked for physical representation (**engram**) of what has been learned
* Lashley concluded that learning did not depend on a single area of the cortex rather **Equipotentiality**: all parts of the cortex contribute equally to learning; and the more cortex, the better
* Newer ideas: Multiple memory systems!
* He was looking at one specific place, but he was cutting in the wrong place. 

H.M. Henry Gustav Molaison

* Subject of a case study that had epilepsy (but studied to take something out that is causing the problem)


* Bilateral medial temporal lobectomy
* Hippocampus, amygdala, adjacent cortex
* Generalized convulsions eliminated, reduced occurrence of seizures
* Normal perceptual, motor, intellectual abilities


* **Could not learn:**
* Digit span + 1 test
* H.M. no more than 8 digit sequence
* Block Tapping Memory Span test
* span of 5 blocks, but not 6 even if repeated 12 x
* Thus, **global amnesia**
* **Did learn**
* Mirror-Drawing test
* Rotary Pursuit test
* Patients with this type of amnesia can learn to read mirror-reversed text, a verbal task

Global amnesia

**A**mnesia for info presented in all sensory modalities

\
* Mild retrograde amnesia 

amnesia for events prior to the surgery

* Anterograde amnesia

* after incident amnesia
* Short-term versus Long-term memories

* Retrograde and Anterograde Amnesia

* Example: after Concussion
* The retrograde amnesia and anterograde amnesia associated with a concussion-producing blow to the head.
* Dont remember before the hit

Sensory buffers 

\
* The briefest and involve sensory impressions 

Short term memory 

Memory of events that have just offered, about 30 seconds or throughout rehearsal

Long term memory 

Memory of events from times further back, days, weeks, months, years

Stages of memory:

* Encoding
* sensory information is encoded into short-term memory
* Consolidation
* information may be consolidated into long-term storage
* Retrieval
* stored information is retrieved

Consolidation affected by:

* Time
* Importance of info/event to be remembered
* Stress → cortisol → glucose → utilization
* Individual differences

Spatial Memory: Morris Water Maze

* Look for hidden pattern in water 
* Hissen platform and rat has to find it 
* Hippocampal dependent memory , hippocampal lesion affects performance use visual cues to see where they are (landmarks)

Radial arm maze

* Tried to get rat once into each arm 
* Working memory error - goes back into same arm

Working memory 

Memory needed to complete the task on which the subject is currently working

Reference Memory 

* Memory of general principles and skills required to perform a task
* Reference memory error 
* Does not follow the rules

Spatial Memory:

* Hippocampal Place Cells and Entorhinal Cortex Grid Cells
* Place cells fire at new spaces 
* **Grid cells** - lead to discovery and nobel prize for two people 
* Fire when animal is moving around open field to give a pattern 
* Give a sense of the area around 
* entorhinal cortex

Long term memory:

* Declarative memory 


* Nondeclearative (procedural) memory 

Declarative memory

\
* Can you answer questions or tell me something 
* Facts and information acquired through learning that can be stated or described; used to answer “what” questions 

\
* Episodic memory
* (= autobiographical memory; for past EVENT)
* Events
* Semantic memory
* (for facts)Stored in diff parts of cortex
* What something is 
* Loss of semantic memory - can not remember the name of something, but can still know how to use it

Nondeclearative (procedural) memory

\
* Implicit memory 
* Can you show me how to do something 
* shown by performance rather than recollection; used to answer “how” questions
* Muscle memory

Types of memory

* Spatial (hippocampus)


* Sensorimotor (cerebellum)
* Response/habit (stratum)
* Emotional (amygdala)

\
* Korsakoff’s syndrome

* Degenerative disease 
* Characterized by memory deficiency and caused by lack of thiamine (vitamin B1) which impedes brain’s ability to metabolize glucose
* If can’t metabolize glucose, then brain can not work 
* Often seen in chronic alcoholism
* Symptoms include apathy, confusion, forgetting, and **confabulation** (taking guesses, falsification to fill in gaps in memory, they think they know the answer but just make something up)
* Initially, anterograde amnesia for explicit episodic memories
* As disease progresses, severe retrograde amnesia

Aging affects memory 

* Memory impairment correlates with shrinkage of the hippocampus during aging.
* Hippocampal formation volume correlate with delayed recall score
* Recall information 
* Dementia 
* General term 
* Drastic failure of cognitive ability, including memory failure and disorientation
* Getting a decline in cognitive ability 
* No particular age attached, but with good health can push later

Alzheimer’s disease

* Ach is deficient 
* A form of dementia characterized by striking cortical atrophy and reduced metabolism
* Characterized by structural damage of the brain
* Begins as memory loss of recent events
* Progressive development of dementia
* Confusion, irritability, anxiety, speech problems, **personality change**
* Memory impairment becomes so extensive that conversation is impossible - both context and prior information are lost
* May not be able to talk 
* Major anterograde and retrograde amnesia
* Symptoms progress because brain is breaking down 
* Brian Atrophy - shrinking brain
* Neuronal degeneration - smaller less connected axon 
* Cellular changes in Alzheimer’s disease 
* Patches of **amyloid plaques** are formed from degenerated neurons by **beta-amyloid** buildup
* **Neurofibrillary** **tangles** form within neurons as abnormal whorls of filaments
* Glymphatic system helps clean up and helps Alzheimer’s 
* Glymphatic system removes toxins in brain during sleep
* Older people sleep less

Where is memory stored ?

* Cortex – Declarative, Priming


* Hippocampus – declarative memory, spatial memory; place cells
* Rhinal Cortex – Object recognition, grid cells
* Cerebellum – classical conditioning (sensorimotor)
* Striatum – habit formation
* Amygdala – emotional memory

\
* Homeostasis 

* the maintenance of a stable, balanced, internal environment
* Ex: ion, calcium levels 

* Motivation 

* Changes in the internal environment can affect **motivation**, the psychological process that induces or sustains a certain behavior
* Drive 
* Hungry is a motivation to eat

\
* Set point

* a single value that the body works to maintain; point of reference in a feedback system
* Ex: normal body temperature, levels of glucose, calcium, O2
* Set Zone
* Range
* Better way to explain optimal range of a variable

\
* Negative feedback 

* Processes that reduce discrepancies from the set point by “feeding back” to reduce the effects of input signals
* Ex: the end product of a chemical pathway will go back to turn off production
* Turn the system off\*\*\*

* Redundancy 

* Our bodies have multiple ways to deal with environmental conditions to maintain constant internal environment 
* Ex: physiological and behavioral response to same variable 

* Allostasis 

* Refers to the adaptive way in which the body changes its set point depending on the situation
* More situational and can be long term 
* The combination of behavioral and physiological adjustments that an individual makes in response to current and predicted behavioral and environmental stressors
* May involve changing the set zone 
* Ex: seasonal changes in body fat lead to change in set point
* Predictive of some environmental conditions 
* Effort of these responses is ***allostatic load***
* What does it take for the animal to change the body 
* Ex: adding fur, shedding fur

\
* Endotherms 

* Warm blooded animal 
* Use physiological mechanisms to maintain nearly constant body temp

* Ectotherms 

* Get most of their heat from the environment 
* Behaviorally going to move back and forth from under the heat lamp and not 

* Maintaining body temp for human 

* 98.6 degrees is normal body temp 
* If air is cold and you need to warm → start a fire, put on warm clothes, shiver
* It if gets warm and you need to cool → sweat, fan yourself, swim, ac

\
* Basic mammalian thermoregulatory system:

* Receptors in skin, body core, hypothalamus detect temp and transmit that info to the spinal cord, brainstem, and hypothalamus.
* Need to send info to spinal cord because spinal cord sends neurons to muscles to move 
* If body temp is outside of set zone, these neural regions can initiate physiological and behavioral responses to return temp to set zone
* Thyroid hormone regulates metabolism which can generate heat (or not)

Two separate thermoregulatory systems in rat hypothalamus

\
* Lesions(putting an electrode in, or chemical in to destroy neuron) in **preoptic area (POA)** impaired __physiological__ responses to cold
* → shivering, constriction of blood vessels; lesion does not affect behavioral responses
* Lesions in **lateral hypothalamus** of rats abolished __behavioral__ regulation of temp
* → turning on heat lamps or cooling fans, bar pressing for desired temp; lesion has no effect on physiological responses
* In order to have a normal physiological and behavioral regulation, the **preoptic area** and **lateral hypothalamus** need to be intact
* Conclude: need POA for physiological responses and LH for behavioral responses

Energy in:

* Through food, drinking


* Q. What happens when you eat a candy bar?
* A. **Glucose** enters the body, gets absorbed into the bloodstream, and goes to wherever it is needed.
* Once it gets into blood, glucose can go wherever and creates ATP
* Q. What if there is excess glucose?
* A. **Insulin** is secreted to bring excess glucose into cells where it is stored as **glycogen** in liver and muscles
* Insulin takes glucose out of blood and puts it in muscles
* B. Glucose also can be stored as fat in adipose tissue (longer term storage)

Energy out: 

\
* 1. Need to eat more
* 2. **Glucagon**(macromolecule of multiple glucose) levels increase to bring glucose(sugar) out of cells
* Break glucagon down 
* 3. Insulin levels decrease
* If there is a lot of insulin, you will keep bringing the insulin in

Type 1 diabetes

* use to be called juvenile diabetes 
* Pancreas does not produce enough insulin
* Lack insulin, either some or none, not much

Type 2 diabetes

* also known as adult diabetes
* Body does not respond to insulin that the pancreas produces
* Non responsive to the insulin
* More difficult to treat  
* Excreting the insulin, so they are constantly hungry

Thirst: Intracellular compartment

The fluid part of the body contained within cells

Thirst: Extracellular compartment

The fluid in the space outside of cells, divided between interstitial fluid and blood plasma

Osmotic Thirst 

* Thirst for water triggered by high extracellular solute concentration, or very salty fluids
* Triggered by high ion/salt
* Osmosensory neurons
* Detected by osmosensory neurons of hypothalamus and OVLT which monitor the concentration of the extracellular fluid
* Regulates thirst 
* Osmotic thirst occurs when the extracellular fluid becomes too salty.
* How does this occur?
* Obligatory water loss, such as respiration and urination (less water relative to solute concentration)
* Eating salty foods (more salt relative to amount of water)
* Both “stimuli” result in water leaving cells by osmosis, which triggers osmotic thirst

Hypovolemic thirst 

* Loss of blood, to total blood volume is lower even though it has the same concentration 
* Thirst results from blood loss
* Concentration of extracellular fluid had not changed; both salt and ions are lost 
* **Baroreceptors in blood vessels and the heart detect a drop is pressure**
* Brain activates responses such as thirst and salt hunger
* Losing salt and water so both may be needed 
* Sympathetic nervous system causes arteries to constrict, and several hormone systems are activated
* Treat with gatorade 

Biological Rhythms 

* Regular fluctuations in any living process
* Variable is TIME, cyclic process with **period** (time interval) that is constant 
* Period = length of time required to complete one cycle
* May be msec, sec, days, months, years
* How long does it take to complete one cycle

**Circadian rhythms**

* have a period of \~24 hours.
* •e.g., sleep-wake cycles, body temp, sensitivity to drugs

**Ultradian rhythms**

* repeat more than once a day, period signif. < 24 hours (e.g., 3, 4, 6 hr periods)
* e.g., bouts of activity, feeding, hormone release

**Infradian rhythms**

* repeat less than once a day, periods are signif. >24 hours
* e.g., reproductive cycles
* Menstrual cycles 
* More than a day

**Circannual rhythms**

* have period of about a year
* e.g., hibernation, migration
* About a year

Diurnal 

Animals active during the day

Nocturnal 

Animals active and awake during night

Zeitgeber period

* The most common synchronizer, or Zeitgeber, is the light-dark cycle.
* In nature, this is the sun, but it can be mimicked in the lab with artificial LD cycles.
* Other Zeitgebers: tides, exercise, meals, arousal of any kind, meals, environmental temperature, etc.
* When to feed the animal, what the temperature is 
* The earth revolves around the sun, once a year and so does weather 
* In the absence of environmental cues, biological rhythms are self-sustaining and have periods similar to (but not exactly the same as) the Zeitgeber period

A phase shift:

*  is a shift in activity in response to a synchronizing stimulus, such as light
* We alter the dark later

**Entrainment**:

* is the process of synchronizing a biological rhythm to a stimulus, so the rhythm has the same period as that of the stimulus 
* The cue that an animal uses to synchronize with the environment is called a zeitgeber, or “time-giver

Constant conditions: Free Runs

* Constant light conditions for the experiment and not changing, a lot of researchers would do dim light 
* animal is maintaining its own cycle without external cues, such as changes in light intensity
* In the absence of cues, humans have a free-running period of approximately 25 hours.

Tau mutation:

* reduction in period length 


* On hamster that showed a rhythm with less than 24 hours
* Tau mutation was causing animals to run earlier

Suprachiasmatic nucleus (SCN)

* In the hypothalamus, above the optic chiasm
* Optic nerves come to optic chiasm and cross up to the thalamus 
* Thought to be biological clock in mammals
* When make lesion in SCN, it will eliminate basic rhythms of drinking, locomotion, and hormone secretion 
* Isolated SCN cells continue to show circadian rhythm for days or weeks 
* Day/night diffs in glucose utilization

light pathway

* In mammals, light information goes from the eye to the SCN via the **retinohypothalamic pathway (tract; RHT**(entrainment pathway)).
* Some retinal ganglion cells project to the SCN.
* Most contain melanopsin, a special photopigment, which makes them sensitive to light. (Non-Rod, Non-Cone cells)

Arrhythmia:

* (still have activity, but timing is off !)
* Not a rhythm 
* Result of making a lesion in the SCN 
* Will not be able to tell dark from light cycle 

Jetlag: rhythms

* Phase shift of circadian rhythm of running wheel activity


* Rhythms can be phase advanced (occur earlier) or phase delayed (occur later)
* Westward Travel : We need to delay our rhythms to adjust to the new time zone.
* Eastward Travel : We need to advance our rhythms to adjust to the new time zone.


* disruption of circadian rhythms due to rapidly crossing time zones
* Stems from mismatch of internal circadian clock and external time 


* Traveling west “phase-delays” our circadian rhythms
* Easier to stay awake because natural rhythms is natural 24 hours 
* Traveling east “phase-advances” our circadian rhythms

Rapid-eye-movement sleep (REM):

* Is characterized by small amplitude, fast- EEG waves; no postural tension; and rapid eye movements.
* When dreaming takes place 

Non-REM sleep: 

* Can be divided into three stages and is characterized by distinctly different EEG waves than REM sleep.
* Everything that isn’t REM is considered non-REM

Beta activity 

(small amplitude, 15-20 Hz) occurs when person is awake and active

Alpha activity 

* (larger amplitude, 8-12 Hz) occurs when person is awake but resting
* Higher amplitude but lower frequency

Delta activity 

(larger waves, 1-3 Hz) when person is sleeping

\
* Stage 1 sleep

* Time spent in alpha rhythm decreases
* Waves of smaller amplitude and irregular frequency begin
* Heart rate slows, muscles relax, eyes roll about slowly
* Lasts several minutes

\
* Stage 2 sleep

* Waves of 12–14 Hz that occur in bursts, called sleep spindles
* Will look for spindles when to determine someone is in stage 2
* K-complexes appear—sharp negative EEG potentials

Stage 3 sleep (slow wave sleep)

* Large-amplitude, very slow waves called **delta waves** appear which occur about one per second
* *Synchronized sleep* with highly synchronized neural activity
* Occurs more frequently in first half of sleep period
* Second half is REM
* All neural activity is working together - synchronized

REM sleep

* Small-amplitude, high-frequency activity, like an awake person
* Desynchronized sleep
* Eyes dart rapidly under closed lids
* Rapid eye movement 
* Muscles relaxed
* Called paradoxical sleep
* Occurs more frequently in later half of sleep period
* Occuring in a period less than 24 hours 
* Low amplitude

Vivid dreams

* Occur during REM sleep 
* Visual imagery; sounds, smells, emotions
* Sense that the dreamer is “there”
* Dreams are very real

Nightmares

long, frightening dreams that awaken the sleeper from REM sleep

Night terrors 

* Sudden arousals from stage 3 SWS
* Marked by fear and autonomic activity

Infant sleep is characterized by:

* Shorter sleep cycles
* More total sleep
* More REM sleep - 50%, which may provide essential stimulation to dev nervous system

As people age:

* Total time asleep declines, and the number of awakenings increases
* Cycles are shorter 
* The most dramatic decline is in stage 3 sleep:
* At age 60, only half as much time is spent in stage 3 as at age 20.
* By age 90, stage 3 sleep has disappeared

Sleep Deprivation

* Experiment: 
* In 1964, 17-year-old high school student Randy Gardner beat the world record for sleep deprivation by staying awake for 264 hours (11 days) without using any stimulants.
* Effects: (partial or total prevention of sleep)
* Increased irritability
* Difficulty in concentrating
* Episodes of disorientation

Energy conservation:

* Muscular tension, heart rate, blood pressure, temperature, rate of respiration are reduced
* When not surviving or chasing prey
* Not expending energy, so saving it  
* Sleep helps animals avoid predators
* Animals sleep during the part of the day when they are most vulnerable
* Where they sleep is tactical 
* Each species’ ecological niche is the unique assortment of opportunities and challenges to which it is adapted

Memory Consolidation 

* Taking information from short term memory and converting to long term memory 
* Sleep during the interval between learning and recall improves retention.
* REM sleep aids memory but is not necessary for all types of learning

* Slow wave sleep:

* The electrical activity in the forebrain showed constant SWS, but no indications of wakefulness or REM sleep—thus, the forebrain alone can generate SWS
* The constant SWS activity in the forebrain is generated by the basal forebrain.
* Neurons in this region become active at sleep onset and release GABA
* GABA activates receptors in the nearby **tuberomammillary nucleus**.
* These GABAA receptors are also stimulated by general anesthetics, which produce slow waves resembling SWS

**Reticular formation**

* wakes up forebrain
* Different groups of nuclei 
* Electrical stim wakes sleeping animals.
* Lesions here produce persistent sleep.
* Axons release **acetylcholine** and **glutamate** which produce excitatory effects to widespread areas of cortex
* \* Reticular Activating System, so named because it increases arousal and vigilance

Locus coeruleus

* Generally cites
* An area of the pons, near the locus coeruleus, is responsible for aspects of __REM sleep__.
* Some neurons in this region are only active during REM sleep.
* They inhibit motor neurons to keep them from firing, disabling the motor system during REM sleep.
* Gaba is involved 
* In basal forebrain 
* Only active during REM sleep

Narcolepsy 

* Hypocretin systems aren't working properly 
* People with narcolepsy:
* Have frequent, intense sleep attacks:
* Last 5 - 30 minutes
* Occur any time of day
* Occur several times a day; every 90 minutes
* Do not go through SWS before REM sleep
* May show cataplexy—a sudden loss of muscle tone, leading to collapse
* Narcoleptic dogs have a mutant gene for the hypocretin receptor.
* Hypocretin normally prevents transition from wakefulness directly into REM sleep.
* Interfering with hypocretin signaling leads to narcolepsy
* Humans with narcolepsy have lost about 90% of their hypocretin/orexin neurons.
* Several different “alertness” drugs are used to manage narcolepsy in humans.

Sleep apnea

* Inability to breathe while sleeping; often results in person waking up many times during the “night” to try to catch their breath; sleepiness during day, impaired attention

Sleep paralysis 

* brief inability to move just before falling asleep or just after waking up.
* May be caused by pontine center continuing to impose muscle paralysis, even after wakefulness

Somnambulism

* (Sleep walking)
* occurs during stage 3 SWS and never during REM (dreaming) when core muscles are totally relaxed

Somniloquy

* sleep talking
* can occur during any stage, often during transition to wakefulness

Sleep-onset insomnia

* difficulty falling asleep; can be caused by situational factors, such as shift work or jet lag

Sleep-maintenance insomnia

* difficulty staying asleep; may be caused by drugs or neurological and psychiatric factors

Termination insomnia 

* wake up too early; may be due to disrupted rhythms; often coincident with depression

Sudden infant death syndrome (SIDS) 

* is the sudden, unexpected death of an apparently healthy infant who stops breathing, usually during sleep.
* Arises from sleep apnea due to immature respiratory pacemaker systems or arousal mechanisms
* Putting babies to sleep on their backs has cut the incidence of SIDS almost in half.

REM behavior disorder (RBD) 

* characterized by organized behavior in person who appears to be asleep.
* Usually begins after age 50
* More common in men
* May be followed by early symptoms of Parkinson’s disease and dementia
* Suggests widespread damage of these diseases begins in brainstem region that imposes muscle atonia

Schizophrenia: Positive symptoms (psychosis):

* abnormal behaviors that are gained—hallucinations, delusions
* Additional symptoms 
* **Delusions** = false beliefs held in spite of contrary evidence
* Belief, in persons mind something is true

Schizophrenia: Negative symptoms

* (emotional and motivational impairments): loss of normal functions 


* Depression, reduced emotional expression
* Do not show emotion

Schizophrenia: Cognitive impairment 

Changes in memory, attention, social perception Schizophrenia

Schizophrenia: Non heritable component 

* Existence of unaffected identical twins implies a non-heritable component
* An integrative model of schizophrenia emphasizes the interaction of genetic factors and stress
* Person could get the trait, but if the environment does not have specific factors, then it will not activate 
* Stressors include:
* Transition from childhood to adulthood
* Prenatal stress, maternal illnesses
* City living - possibly due to pollutants, exposure to other diseases, crowded conditions, tense social interactions
* Study: people and where they lived → could be pollutants, exposure, too many people living in close quarters can be stressful

Brain abnormalities in patients with schizophrenia:

\
* **Enlarged lateral ventricles**
* Cortical abnormalities
* Structure and function of the corpus callosum
* Accelerated cortical thinning
* Same genes, but genetic and epigenetic factors influence
* Loss of gray matter (cell bodies)

**Hypofrontality hypothesis:**

frontal lobes are underactive in people with schizophrenia

Chlorpromazine 

* Antipsychotic discovered in early 1950s
* Powerfully reduced positive symptoms of schizophrenia
* Quickly replaced lobotomy treatment for schizophrenia
* All first-generation antipsychotics (typical antipsychotic) drugs block postsynaptic dopamine D2 receptors 
* Had to come up with the second generation when not everyone was responding to the first 
* Antagonist 
* Antipsychotic drugs can have side effects:
* Dyskinesia—initial, maladaptive motor symptoms; disappear when dose is reduced
* Tardive dyskinesia—late onset; repetitive, involuntary movements; irreversible; may be due to dopamine receptor supersensitivity
* Supersensitivity psychosis—marked increase in positive symptoms of schizophrenia upon discontinuation of antipsychotic drugs

\
* The dopamine hypothesis 

* Proposed that schizophrenia is caused by an excess of either dopamine release or dopamine receptors
* Problems with the dopamine hypothesis:
* Drugs block D2 receptors much faster than symptoms are reduced
* Some drugs that are effective actually increase dopamine levels in the frontal cortex