Lecture 5 Overview(1) Learning and memory structures(2) Learning (conditioning)(3) Forms of memory

Simple forms of learningsensitization / habituation (Applysia)Rabbit Eye Blink

Molecular mechanismsHippocampus circuitsLTP / plasticityTheta / gamma patterns40Hz waves & the “binding problem”

This image from the hippocampus shows smaller glial cells (the small ovals) among neurons (larger, with more filaments). The hippocampus is known to play a major role in memory formation.

Parahippocampal gyrusSpatial memory

Fear learning Anterograde amnesia

Alzheimers-like symptoms

No new learning

Connect new learning with long term memory, blocks LTP

Error detection, consciousness?

Sensory input;Alertness related to learning and memory

Sensory integration & input to hippocampus

http://neuroscience.uth.tmc.edu/s4/chapter07.html

http://neuroscience.uth.tmc.edu/s4/chapter05.html

A. Semantic memoryB. Episodic memoryC. Implicit memory

Facts, meanings, concepts, symbols, abstract knowledge (frontal & temporal lobes)

Recall of events, chonological experiences. (hippocampus constructs a “memory” from the element)

Spatial memory remains in hippocampus, but distant memories involve neocortex.

Implicit memory is about procedures (knowing how to do it without recalling the learning experience)

striatum neocortex amygdala cerebellum reflex path (brain stem)

Long term memory types

Medial temporal lobe

Videos on:

Classical conditioning (pavlov, aplysia)

Operant conditioning (skinner, family guy)

SIMPLEST LEARNING Applysia

Model for sensitization and habituation

Entire nervous system of this animal only has about 10,000 cells.

Threshold for molecular changes in “brain” is 5 pokes.

Long-term effect:More synapses and more release at them

Molecular Pathway:5HT (serotonin)G-proteinAC (adenylyl cyclase)Makes cAMPPKAMAPKCREB-1 / CREB-2Gene transcription(new synapses, new receptors)Also phosphorylation of receptors to alter activitiy.

Molecular changes with sensitization

Motor neuron has more receptors when sensitized

And fewer receptors when habituated / desensitized

Second messenger systems (used in many parts of nervous system, not just learning and memory)

receptor-cAMP-AC-PKA

Ion channel-Ca2+-PKC

Receptor-Gq/11-PLC-DAG-PKCAnd IP3 changes calcium signaling

The DAG + IP3 second messenger system

Gai / Gao– inhibits AC - less cAMP

G β/γ – closes calcium channels

Gt / Ggust – activates phosphodiesterase to dephosphorylate internal proteins (inhibitory)

Gas – activates AC - increases cAMP(commonly coupled to metabotropic receptors that bind NE β1/2, 5-HT4/6/7 , DA D1/5, Histamine H2

Golf – olfactory, activates AC

Gq/11 – activates phospholipase C and creates DAG/ IP3.

G12/13 – activates Rho family of GTPases

http://en.wikipedia.org/wiki/Heterotrimeric_G_protein

αβ γ

Rabbit eye blink conditioning –

The delay between the two stimuli (puff of air and tone) was significant factor in determining what part of the brain controlled the learning.

Immediate 50ms = brain stem (pons)

½ second or longer activates hippocampus short term memory

Reveals a set of overlapping memory systems all over brain depending on context cues.

Entorhinal cortex

Complex learning

Hippocampal Trisynaptic loop

(core of learning and memory)

Perforant path (2 parallel routes from EC to hippocampus via subiculum and DG)

Mossy Fiber Pathway (DG CA3)

Shaffer Collaterals (CA3 CA1)

LTP

Long term potentiation

Synapses are more active after repeated stimulation (high frequency “tetanus” of action potentials ~40-100 HZ) for 1s duration.

LTD

Long term depression

Opposite effect, triggered by frequent (10mins) with low-frequency (1Hz) stimulation.

Synapses change response with activity types = plasticity

Receptor subtypes are rapidly endocytosed / placed in membrane with LTD / LTP

The slope plotted here

( Field potential recordings are opposite direction of action potentials because current flow is opposite )

Unsilencing of synapses (NMDA without AMPA)

When glutamate is the neurotransmitter in the synapse…

Of LTP

cancer

Dendritic spines also change morphology as permanent plasticity change

Learning / Memory theory:LTP induced changes in spine morphology

Brain waves: “rhythmic oscillations in cell electrical potential”

40 Hz gamma = significant for whole brain

4-10 Hz theta = learning related

Deep sleep / coma

Hypothesis: oscillations coordinate brain activity

“Place cells”

Spatial firing patterns of seven place cells recorded from a single electrode in the dorsal CA1 layer of a rat.

“phase precession” of theta rhythm– anticipation signal

Innervation of pyramidal cells by 12 types of GABAergic interneuron and interneurons by 4 types of interneuron specific cell in the CA1 area of the hippocampus

Expression channelrhodopsin in certain cell types + light stimulus to induce spiking = gamma rhythms

The gamma waves were most apparent at a frequency of 40 Hz; this indicates that the gamma waves evoked by FS manipulation are a resonating brain circuit property. This is the first study in which it's been shown that a brain state can be induced through the activation of a specific group of cells.

We causally tested these hypotheses in barrel cortex in vivo by targeting optogenetic manipulation selectively to fast-spiking interneurons. Here we show that light-driven activation of fast-spiking interneurons at varied frequencies (8-200 Hz) selectively amplifies gamma oscillations. In contrast, pyramidal neuron activation amplifies only lower frequency oscillations, a cell-type-specific double dissociation. We found that the timing of a sensory input relative to a gamma cycle determined the amplitude and precision of evoked responses. Our data directly support the fast-spiking-gamma hypothesis and provide the first causal evidence that distinct network activity states can be induced in vivo by cell-type-specific activation.

FS cells are inhibitory interneurons in the somatosensory cortex.

Humans have a persistent 40Hz brain wave oscillation that might be part of information flow, coordination, processing.

The medial septal area projects to a large number of brain regions that show theta modulation, including all parts of the hippocampus as well as the entorhinal cortex, perirhinal cortex, retrosplenial cortex, medial mamillary and supramamillary nuclei of the hypothalamus, anterior nuclei of the thalamus, amygdala, inferior colliculus, and several brainstem nuclei (Buzsáki, 2002). 

Frequency is determined by a feedback loop involving the medial septal area and hippocampus (Wang, 2002).

The phase and amplitude of theta change in a very complex way as a function of position within the hippocampus. The largest theta waves (~1mV oscillations), however, are generally recorded from the vicinity of the fissure that separates the CA1 molecular layer from the dentate gyrus molecular layer.

More Complex Learning

More Complex Learning

1. Types of Memory2. Learning modes3. Molecular mechanisms for

each1. Pathways (CREB, PKA,

Ca2+)2. Anatomy3. Firing patterns (theta,

gamma burst)4. Pharmacology

1. Blocking / facilitating learning