Neurobiology of Learning and Memory

Exam 1

What makes a cell specific?

Which genes are expressed

Proteins give the cell its specific properties

Types of neuronal communication

Electrical and Chemical

Define Electrical neuronal communication

Movement of ions changes membrane potential and generates action potentials

Define Chemical Neuronal communication

Neurotransmitters are released at synapses and bind receptors on postsynaptic cells

What are the three important players regulating membrane potential?

Ions, the phospholipid bilayer, and proteins

What are the two forces regulating ion movement?

Diffusion and electrostatic forces

What is the resting membrane potential?

The voltage across a resting neuronal membrane ~65mV

What is an action potential?

An all-or-none electrical signal traveling down an axon

How is an action potential initiated?

Sufficient depolarization brings the membrane to threshold

How is stimulus intensity encoded by action potentials?

By action-potential frequency and firing pattern

How is neurotransmitter released?

Action potential → terminal depolarization → Ca2+ influx → vesicle fusion → neurotransmitter release

What is synaptic transmission?

The biological process by which a neuron communicates with another cell cross a specialized gap called a synapse

Example of synaptic transmission

Neurotransmitter release, diffusion across the cleft, and postsynaptic receptor binding

What determines a neurotransmitter’s postsynaptic effect?

The receptor it binds to

What are transmitter-gated ion channels?

Fast receptors that directly open ion channels when neurotransmitter binds

How do GPCRs work?

Neurotransmitter activates a G protein that affects proteins and signaling pathways

What is a first messenger?

An extracellular signal such as a neurotransmitter

What is a second messenger?

An intracellular signal such as Ca2+ or cAMP

What do intracellular signaling cascades do?

Amplify signals and alter proteins, channels, cell processes, or gene expression

What can signaling cascades ultimately change?

Protein activity, ion channels, cellular processes, and gene expression

What is a kinase?

An enzyme that phosphorylates proteins

What is a phosphatase?

An enzyme that dephosphorylates proteins

What are postsynaptic potentials?

Graded membrane-potential changes; EPSPs depolarize and IPSPs hyper-polarize

What is learning?

A process initiated by experience that acquires new information

What is memory?

The persistence of learning that can be revealed later

Why are learning and memory theoretical concepts?

They are inferred from behavior and cannot be directly observed

What is the psychological approach to learning and memory?

It studies how experience influences behavior

What is the neurobiological approach to learning and memory?

It manipulates brain processes and measures resulting behavior

What did Ebbinghaus manipulate?

Practice amount, spacing, and delay between learning and testing

What did Ebbinghaus find about practice?

More practice improved later recall

What did Ebbinghaus find about spacing?

Spaced practice was better than massed practice

What did Ebbinghaus find about learning-test delay?

Shorter delays produced better recall

What is the forgetting curve?

Recall falls rapidly at first and then becomes relatively stable

What theories came from the forgetting curve?

Single trace theory and dual trace theory

What is single-trace theory?

One memory trace gradually weakens as time passes

What is dual trace theory?

Two traces exist with different decay rates: short-term and long-term

What is Ribot’s law?

Older memories are more resistant to disruption than newer memories

What does Ribot’s law imply?

Different kinds of memory rely on different memory systems

What is anterograde amnesia?

Inability to acquire new memories after brain damage or disease

What is retrograde amnesia?

Loss of memories formed before brain damage or disease

What was William James’s memory theory?

After-image → primary memory trace → secondary memory trace

What was Golgi Reticulum Theory?

The nervous system forms one continuous interconnected network

What was Ramon Y Cajal Neuron Doctrine?

Neurons are separate, discrete cells

What is the Synaptic Plasticity Hypothesis?

Experience can modify synaptic strength

What is classical conditioning?

Learning an association between a conditioned stimulus and an unconditioned stimulus

In Pavlov’s experiment, what is the Unconditioned stimulus?

Food

In Pavlov’s experiment, what is the Unconditioned response?

Salivation to food

In Pavlov’s experiment, what is theIn Pavlov’s experiment, what is the conditioned stimulus?

The bell

In Pavlov’s experiment, what is the conditioned response?

Salivation to the bell

What is the operant conditioning?

Learning in which voluntary behavior is shaped by reinforcement

What is a cell assembly?

A distributed circuit of connected neurons representing a concept or experience

How do cell assemblies contribute to memory?

Experience changes connectivity among neurons in the assembly

Where are memories stored?

Across the neural systems engaged by the experience

What are memories physically?

Changes in connectivity among groups of neurons

What is synaptic modification?

An activity dependent change in synaptic strength or structure

How does synaptic modification support memory?

It changes communication within cell assemblies

What is a memory trace or engram?

A sustained neural representation of an experience Q

What is LTP?

Persistent, activity-dependent strengthening of synaptic transmission

How is LTP studied?

By electrophysiologically comparing synaptic responses before and after strong stimulation

How is LTP studied in a hippocampal slice?

Weak baseline stimulus → strong inducing stimulus → weak test stimulus

What does an intracellular recording measure?

EPSPs from one postsynaptic neuron

Why are intracellular EPSP positive-going?

Positive ions enter the recorded neuron

What does an extracellular recording measure?

A field EPSP from a population of neurons

Why are extracellular fEPSPs negative-going?

Positive ions leave extracellular space as they enter neurons

What does a larger intracellular EPSP amplitude mean?

Stronger synaptic transmission

What does a larger or steeper fEPSP mean?

Stronger synaptic transmission

What is the fiber volley?

The extracellular signal from action potentials in stimulated presynaptic axons

What is the trisynaptic hippocampal pathway?

Perforant path → dentate gyrus → mossy fibers → CA3 → Schaffer collaterals → CA1

Why is the hippocampus useful for studying LTP?

It is important for episodic memory and has clear anatomical organization

What is an fEPSP?

A field excitatory postsynaptic potential recorded extracellularly

What does an fEPSP measure?

Strength of a population of synapses

How do you read an fEPSP waveform?

Steeper slope or larger absolute amplitude means stronger synaptic transmission

What are major principles of LTP?

Duration varies, molecular mechanisms determine duration, and LTP occurs in stages

What contributes to LTP duration?

Stimulation strength/pattern and the molecular pathways recruited

What is LTD?

An activity-dependent decrease in synaptic strength

What is LTD dependent on?

Low-frequency stimulation, low postsynaptic Ca2+, phosphatases, and AMPAR internalization

What are the two main glutamate-receptor classes?

Ionotropic and metabotropic

What are the ionotropic glutamate receptors?

AMPA, NMDA, and kainate

What are the metaotropic glutamate receptors?

mGluR1-8

Ionotropic vs metabotropic receptors?

Ionotropic receptors are channels; metabotropic receptors use G proteins

What ion mainly passes through AMPARs?

Na+

What ions pass through NMDARs?

Na+ and Ca2+

How do AMPARs contribute to LTP?

They depolarize the neuron and support stronger synaptic responses

How do NMDARs contribute to LTP?

They allow Ca2+ influx needed for LTP induction

What is a ligand?

A molecule that binds selectively to a receptor

What is an agonist?

A ligand that activates a receptor

What is an antagonist?

A ligand that blocks receptor activation

Competitive antagonist:

Blocks the ligand binding site

Noncompetitive antagonist:

Does not act on the ligand-binding site

LTP induction:

Initiates LTP

LTP expression

Strengthened synaptic response

Which receptor is key for LTP induction?

NMDA receptor

Which receptor is key for LTP expression?

AMPA receptor

What happens during AMPAR trafficking?

AMPARs are delivered, diffuse into PSD, are trapped, or undergo endocytosis

Why is glutamate important for LTP?

It activates AMPARs and NMDARs

What two events open the NMDA receptor?

glutamate binding and postsynaptic depolarization removing the Mg2+ block

What contributes to LTP induction?

Strong stimulation → AMPAR depolarization → NMDAR opening → Ca2+ influx

What contributes to LTP expression?

Increased AMPAR number/function in the PSD

Why is Ca2+ important for LTP induction?

It is a second messenger that activates plasticity enzymes

What is constitutive AMPAR trafficking?

Continuous cycling of AMPARs into and out of dendritic spines