learning and memory

learning

a relatively permanent change in behavior due to experience

memory

the means by which past experience is drawn on to guide/direct behavior or thoughts in the present

learning and memory

endow us with the flexibility to adapt to an ever-changing environment

1. Learning and memory occurs in stages:

   1. Acquisition of information

   2. Consolidation of storage of information

   3. Retrieval of information

2. Timing of hormonal manipulation is critical 

   1. Acquisition - prior to first exposure to task

   2. Consolidation - at the point between learning and retest 

   3. Retrieval - immediately before re-test 

Hormones may also affect non-mnemonic factors which could indirectly affect learning and memory: attention, motivation, sensory responsivity and motor capabilities

Why is it difficult to determine the effects of hormones on learning and memory?

1. Acquisition

2. Consolidation

3. Retrieval

stages of learning/memory

Hormone administration prior to first exposure to a task

acquisition

Hormone administration between learning and re-test

consolidation

Hormone administration immediately before re-test

retrieval

non-mnemonic factors

performance factors - factors that indirectly affect learning/memory 

Attention, motivation, sensory responsivity and motor capabilities

examples of non-mnemonic factors

Cognitive Tasks - use tasks for which the underlying neural circuitry has been partially or fully elucidated

How can hormonal effects on cognition be examined?

hippocampus and amygdala

Many of the tasks used in studies of hormones and cognition depend on neural circuits involving the BLANK, BLANK and various cortical regions – all areas are critical for learning, memory and emotions; contain receptors for several different hormones or receive input from other brain regions that express hormone receptors

radial arm maze

Spatial task used commonly for learning/memory tasks in behavior endocrinology; the subject is allowed to wander until all food sites have been found; the subject learns to avoid arms that never have food and to avoid revisiting arms that it had previously visited on that day; locate food sites by using spatial cues in the room

advantage of radial arm maze

easy to perform

disadvantages of radial arm maze

many training trials required to achieve steady performance so hormonal effects must be assessed over days and sometimes weeks which makes it difficult to isolate the effects of hormones to one stage of learning and memory

morris water maze

Spatial task used commonly for learning/memory tasks in behavior endocrinology; makes use of the rats natural tendency to escape to dry land if it is placed in the wate

advantage of morris water maze

 easy to perform and quickly learned

disadvantages of morris water maze

its an aversively motivated task so the stress of training and testing may activate other hormonal systems not under study

active avoidance

Animal must act to avoid a noxious stimulus

passive avoidance

Animal must suppress a behavior that would otherwise be exhibited (must learn to stay put)

Fear conditioning

type of learning where a neutral stimulus becomes associated with an aversive event, causing it to trigger a fear response

advantages of fear conditioning

 easy to perform, quickly learned and memory retained for many days therefore used extensively to examine stages of memory when hormones may be acting

disadvantages of fear conditioning

it is an aversively motivated task so that stress itself activates other hormonal systems that may confound interpretation

social recognition

Makes use of the animal’s tendency towards olfactory investigation of novel co-specifics

• Two rats are allowed to interact and smell one another for several minutes; after a delay in which they are separated from one another, they are returned for a second meeting

  • If recognition occurs - subject spends less time investigating familiar stimulus animal

  • If no memory present - subject investigates familiar animal a lot as if it were novel

advantages of social recognition

 easy to perform and quickly learned and memory retained for many days

disadvantages of social recognition

hormones can affect olfactory processing so it is necessary to be careful that hormones are altering cognitive and not just sensory mechanisms

classical eyeblink conditioning

a learning process where a neutral stimulus (CS), like a tone, is repeatedly paired with an unconditioned stimulus (US), such as eyelid shock, which naturally triggers an eyeblink (UR). Over time, the neutral stimulus alone begins to elicit a conditioned response (CR) of an eyeblink before the eyelid shock occurs, demonstrating associative learning

yerkes-dodson law

Optimal performance occurs at moderate levels of stress or arousal; if stress/arousal is too high or too low, learning is adversely affected

epinephrine

1. enhances performance on a variety of learning and memory tasks; these effects are dependent on dose and time 

   1. Moderate doses are more effective than low/high doses

   2. There is greatest enhancement observed shortly after training than before, during or long afterwards → suggests that epinephrine may be acting on memory storage

EPI and memory

1. Influences memory by making noxious stimulus more salient 

   1. Evidence: animals perform better in avoidance tasks if receive moderate rather than mild shock; if the mild shock is paired with EPI treatment, the animal exhibits optimal training

EPI and BBB

1. EPI does not cross the Blood Brain Barrier - EPI must affect some processes outside of the brain that subsequently influences learning and memory 

peripheral receptor hypothesis

1. EPI activates peripheral receptors that interact directly with the brain 

2. Evidence - memory enhancing effects of EPI can be blocked by peripheral blockade of beta adrenergic receptors or by infusing the receptors directly into the amygdala

glucose hypothesis

1. EPI affects memory via its effects on blood glucose; increasing glucose availability to the brain

2. Evidence - just like EPI, the memory enhancing effects of glucose follow the inverted U shaped curve and are time dependent 

   1. Moderate doses are most effective

3. How does glucose affect memory → elevated blood glucose permits more glucose to enter neurons, this releases the release of ACH into synapses

It follows an inverted U-shaped curve—moderate CORT enhances learning/memory, while very low or very high levels impair it.

What is the relationship between CORT (glucocorticoid) levels and learning/memory?

Enhances learning and memory.

How does acute stress affect learning and memory?

Impairs learning and memory.

How does chronic stress affect learning and memory?

Yes—effects depend on factors such as sex, type of stressor, and type of task

Are there exceptions to stress effects on cognition?

It enhances memory consolidation, mimicking acute stress—improves avoidance learning when given right after training.

What effect does acute glucocorticoid administration have on memory consolidation?

It impairs memory retrieval.

What effect does acute glucocorticoid administration have on memory retrieval?

• Males: Acute stress enhances classical eyeblink conditioning.

• Females: Acute stress impairs classical eyeblink conditioning.

How does acute stress affect learning/memory in males vs females?

• Males: Chronic stress impairs spatial memory.

• Females: Chronic stress enhances spatial memory on the Radial Arm Maze.

How does chronic stress affect spatial memory in males vs females?

• Acute stress: ↑ dendritic spines in male hippocampus; ↓ dendritic spines in females.

• Chronic stress: ↓ dendritic length and branching in male hippocampus.

What brain changes accompany sex-dependent stress effects?

Patients with Cushing’s syndrome (chronically high CORT) show reduced hippocampal volume and impaired memory.

Give a human example showing glucocorticoid effects on memory.

• Females: Use landmark cues.

• Males: Use geometric cues.

What spatial strategies do males vs females use?

• Testosterone treatment before day 10 → masculinizes spatial ability and improves RAM learning.

• Castration at birth → impairs RAM learning.

• Blocking aromatization (aromatase inhibitor) → males learn more slowly and use mixed cues → estrogen conversion required for masculinization.

How do hormones early in development organize sex differences in spatial abilities?

What effects do androgens have on learning/memory in rodents?

• Castration can impair spatial abilities.

• Testosterone replacement can restore/improve performance.

Yes—low testosterone in men (hypogonadism/aging) is linked to poorer cognition and can be improved with testosterone supplementation.

Do androgens affect learning and memory in humans?

Low testosterone may increase Alzheimer's risk; supplementation can improve spatial and verbal memory in Alzheimer’s patients.

How is testosterone related to Alzheimer’s disease risk/performance?