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Neuroscience 506, Kenyatta University
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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