CBNS 126 Lecture 1 (Intro and Mind to molecules)

Major question in neuro

• How is memory encoded? – memory acquisition.

• How is a short-term memory converted into a long-lasting memory? – memory consolidation.

• Where is memory stored? – memory location.

• What is a physical record of memory? – memory trace.

• How is memory retrieved? – memory recall

The four c’s

• connection

• cognition

• compartmentalization

• consolidation

Connection

The most basic level of analysis of memory, the basic nature of the circuitry of the brain

how 2 neurons communicate

figure out how connected, then study synaptic plasticity

• the elements of information processing

• how neurons communicate to each other in the service of memory

Cognition

refers to the psychological aspect of neuroscience

• nature of memories at the highest level of analysis, psychological level

Compartmentalization

memory localization

different memories are accomplished by specific:

• modules

• circuits

• pathways

• systems

notion of compartmentalization 

there are many interconnected cognitive processing centers in the brain that are processing newly acquired information.

ex:

• amygdala is required for fearful memories establishment and storage. (temporal, in hippocampus)

• Formation of memories about context and space involves information processing in hippocampal-cortex memory system (temporal lobe)

Consolidation (SM to LM) recall muler and pilzecker

when and how memories become permanent

Memories are initially labile

– conversion into long lasting memories

Memory consolidation can be study at two different level of analysis:

1. Memory fixation: cellular/molecular mechanism (synaptic plasticity)

• Occurs within the first minutes to hours after learning.

• Involves changes at the synapse (synaptic plasticity).

• When neurons are repeatedly activated together, their connections become stronger (Hebbian learning).

• Key processes:

  • Long-Term Potentiation (LTP): Strengthens synaptic transmission between neurons.

  • Protein synthesis: Needed to stabilize new synaptic changes.

  • Structural growth: New dendritic spines and synapses may form.

• This level “locks in” the trace of the memory at the neural connection level.

1. Memory reorganization

• Occurs over days, weeks, or even years.

• The memory gradually becomes independent of the hippocampus and is stored across the cortex.

• Integration: New information is woven into existing knowledge networks (schemas).

• Interactions: Involves communication between the hippocampus, neocortex, and other brain regions.

• Often supported by sleep—especially slow-wave sleep, which helps transfer memories to long-term storage.

• This process gives memories more meaning, context, and permanence.

Loss of memories can lead to serious neurocognitive issues 

• alzheimer’s

• huntingtons

• mental retardation

• weakening memory with age (so many factors)

• 50% chance to age successfully and normally

** weaking happens regardless (a tad)

Learning and Memory

learning: acquisition of new information

memory: retention of learned information

• way info is stored may change over time

5 memories

1. acquisition (encoding)

2. consolidation (SM to LM)

3. location (stored)

4. trace (physical record of it)

5. recall (retrieval)

Declarative memory

• explicit and conscious

• facts, events, episodic from life, semantic

• hippocampus dependent (system level)

Nondeclarative memory

• implicit and unconscious

• procedural: skills, habits, behaviors

• basal ganglia and cerebellum (motor)

Multidisciplinary study of learning and memory

Philosophy

• What aspects of the mind’s knowledge are innate, and to what extent can the experience influence that innate organization?

Psychology

• How does memory work?

• Are there different kinds of memory?

Biology

• What are the brain structures recruited during L&M?

• Where do we store what is learned as memory?

• Can memory storage be resolved at the level of individual neural cells?

modern neuroscience is the combo of biology and psych

Memory as a psych process: Herman Ebbinghaus 1880s

established experimental and quantitative ways to study memory

• verbal memory

Study: made 2300 new syllables (lacked meaning for participants)

• learning: studied the number of repetitions and recollection after various delays 

• Method: Self-experiments with nonsense syllables

• Measure: Savings → faster relearning after delay

• Findings:

  • Forgetting curve → rapid initial loss, then slows

  • Savings effect → memory traces persist

  • Spacing effect → spaced learning > massed

• Conclusion: Memory loss is systematic; relearning easier than initial learning

Found:

1. memories have different span (SM and LM)

2. repetitions make memories last longer

Memory as a psych process: George Muller and Alfons Pilzecker (1892-1900)

came up with the notion that short lived memories can be consolidated with time

“learning does not induce instantaneous permanent memories but that memory takes time to be fixed or consolidated”

“memory remains vulnerable to disruption for some time after learning

• used a list of nonsense syllables like ebbinghaus

Study:

After learning the first list, some participants:

1. Rested for a short period before learning a second list.

2. Immediately learned a second list with no delay

Found:

• When participants were tested later on the first list, recall was much better if there had been a delay before the second list was introduced.

• If the second list came right away, recall of the first list was significantly worse

Consolidation needs to occur to stabilize memory

Memory as a psych process: Sergei Korsakoff

Korsakoff’s syndrome: 

• Cause: Chronic thiamine (vitamin B1) deficiency, often due to long-term alcoholism

• Brain damage: Especially to medial diencephalon (thalamus, mammillary bodies)

• Symptoms:

  • Severe anterograde amnesia (can’t form new memories)

  • Some retrograde amnesia (loss of past memories)

  • Confabulation (making up stories to fill memory gaps)

  • Apathy, lack of insight

Developed idea: How does this function affect the brain and how does the loss of function predict what area caused it

**too broad

Brocha did better job 

Memory as a psych process: William James

Provided distinction btwn SM and LM

Short-term memory

• lasts seconds to minutes, and is essentially extension of present moment

• E.g. looking up a phone number to call

Long-term memory

• can last weeks, months or even lifetime.

• E.g. reaching into the past, childhood memories

Behaviorist revolution: Procedural learning (non declarative)

motor response in response to sensory input

Learning:

1. nonassociative

2. associative

👉 Key difference:

• Habituation = tuning out irrelevant/repeated stimuli.

• Sensitization = tuning in more strongly to stimuli, especially after something intense or threatening.

nonassociative: habituation (1 stimuli)

learning to ignore stimulus that lacks meaning 

ex:

• Living near train tracks → at first the noise is loud and distracting, but over time you stop noticing it.

• A ticking clock that fades into the background.

nonassociative: sensitization (1 stimuli)

An increase in responsiveness to a stimulus, often after an intense or noxious one.

ex:

• Hearing a sudden gunshot → you become hyper-alert, so even small noises (like footsteps or a door creak) trigger a strong reaction.

• After a scary movie, every little sound makes you jump.

associative: classical conditioning

THE BASIS OF LEARNING

Pavlovian conditioning occurs when a neutral stimulus (CS) is repeatedly paired with an unconditioned stimulus (US) until the conditioned stimulus (CS) alone elicits a conditioned response (CR).

laid the foundation for the paradigm that a stimuli can formulate a response (relationship), which led to other scientists to modulate this

basis of learning (Pavlovian conditioning cont.)

We learn something through the relation of it to something (has consequences on our knowledge)

We learn to predict future based on experience (memory)

• stimulus predicts output

• measures relationship

IMPORTANCE:

**u can find what circuits are part of this process (molecular, cellular, and cognitive basis)

• can find the circuit and track it

• Once you find a circuit, you find a neuron that detects the presence of these 2 stimuli

**this paradigm can be applied to other things

Memory as a neural process: Brain and neuron anatomy

**recall brain anatomy if confused

1. Neurons

2. Glia cells

Memory as a neural process: Golgi stain

Camillo Golgi started flawed neuron doctrine

**argued that the nervous system is a continuous network of interconnected fibers (like a web), rather than being made up of discrete, individual cell

• stain allowed one to see whole neuron

• concluded that have important structural aspects

• didn’t know abt the synapse

Stain showed:

• soma

• neurites: axons and dendrites

Memory as a neural process: Golgi stain

Santiago Cajal contributed to the neuron doctrine

• discovered neural circuitry

• neurons communicate by contact not continuity

Memory as a neural process: Golgi and Cajal

set up idea to study neurons (didn’t find exact names)

• didn’t know about AP’s

• found structure must predict function

• wtvr these neurons do must be important

Cajal’s neuron doctrine stated that the nervous system is made up of discrete, individual cells (neurons) that communicate with each other at specialized contact points (later called synapses), rather than being one continuous web.

Memory as a neural process: chemical synapses

pre:

• mitochondria: vesicles release neurotransmitter

• have vesicles

post:

• receptors

Memory as a neural process: Jerry Konorski (1903-1973)

**neural plasticity

proposed first theory of associative learning as a result of long-term synaptic plasticity

"The plastic changes would be related to the formation and - multiplication of new synaptic junctions between the axon terminals of one nerve cell and the soma (i.e. the body and the dendrites) of the other"

• first person who coined the term “neural plasticity”

• discovered type II conditioned reflexes which are now known as operant conditioning or instrumental conditioning

proposed existence of gnostic neuron, called 2 years later by Jerry Lettvin a grandmother cell (a hypothetical neuron that represent complex but specific object of concept like a some one face

Memory as a neural process: Donald Hebb (1904-1985) Hebbian Theory 1949

(often summed up as “cells that fire together, wire together”) states that when one neuron’s firing consistently contributes to the firing of another, the connection (synapse) between them is strengthened, making future communication more efficient.

Biological revolution: classical conditioning in fruit fly drosophila

Seymour Benzer

developed the genetic screen for memory genes. He found that fruit flies are capable of associative classical conditioning. They found mutants that have deficiency in memory. All mutants had deficiency in PKA signaling pathway.

Examples:

-rutabaga - mutation in Adenylyl Cyclase

-DCO – mutation in catalytic subunit of PKA

PKA: protein kinase A pathway is critical for pavlovian conditioning

multiple brain systems for memory storage

Central sulcus

groove in the cerebral cortex that separates the frontal lobe from the parietal lobe and the primary motor cortex from the primary somatosensory cortex

sylvian fissure (lateral sulcus)

begins near the basal forebrain and extends to the lateral surface of the brain separating the frontal and parietal lobes superiorly from the temporal lobe inferiorly

cerebellum

part of the brainstem located at the back of the head below the occipital lobe

• Motor coordination: Refines and smooths movements using sensory and motor input.

• Balance & posture: Maintains stability and corrects imbalances.

• Muscle tone: Regulates stiffness and relaxation of muscles.

• Motor learning: Adapts and learns new motor skills.

• Cognition: Involved in attention, emotion, and social behavior.