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Biological Memory

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North Akara

on 19 November 2014

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Transcript of Biological Memory

Neurodegeneration
What we know & Where we are going
Memory clearance
BIOLOGICAL MEMORY
What we know and Where we are going
A supplement to the oral part of the Ph.D. Qualifying Examination in Neuroscience
Research Center for Neuroscience | Institute of Molecular Biosciences | Mahidol University
Akara Metasuk
23 August 2012
History
Classification
Anatomical Structure
Molecular Structure
Development
Hormones
Plasticity
Degeneration & Aging
Drugs of Abuse
Manipulation
Models & Algorithms
Forthcoming Studies
Public costs on disease management
Education
systems

Media
Entertainment

Functional
food

Books
Workshops

&
&
The History of the Studies of Memory
Classification of Memory and the processing
Gross Structure of the Brain
Involved in Memory Processing

Cellular and Molecular Structure of the Brain
Involved in Memory Processing

Brain Development and Memory Functions During Brain Development
Hormonal Regulations of Memory
Neurotransmitting Chemicals
Known to be Related to Memory Processing

Effects of Cellular Changes to Memory:
Neuronal Plasticity and Apoptosis

Neuropathology/Psychiatry of Memory and Brain Aging
Drug Addiction and Memory
Medicines, Chemicals and Activities for Memory Booster,
Memory Alteration and Memory Clearance

Models and Algorithms for the Study of Memory and Cognitive Neural Prosthesis
+ Student-based learning
+ Project-based learning
+ Seminars
+ Home schools

+ Educational programs
+ Brain training
+ Emotiv, NeuroSky, Neurowear, intendiX

Mind
Monism
Dualism
Memory
Learning
Idealism
Physicalism
Neutralism
René Descartes: Seat of the mind
The ability to store, retain and recall an information.
The change of a behavior as a result of acquiring an information.
Habituation
Sensitization
Imprinting
Conditioning
Classical
Conditioning
Operant
Cajal: No new neuronal cells.
Hebb: Neuronal connections
Kandel: Structural changes
Forward
Backward
Reinforce
Punish
Sensory
Memory
Short-Term
Memory
Long-Term
Memory
Atkinson-Shiffrin
Multi-Store Memory Model
Baddeley-Hitch
Working Memory Model
Central
Executive
Phonological
Store
Visuo-Spatial
Sketchpad
Episodic Buffer
100-500 ms
< 1 min
lifetime
Consciousness, attention
Rehearsal
Encoding
Storage
Recall
Societal concern?
Image source:
http://www.chicagopersonalinjurylawyersblog.com/Structure%20of%20the%20brain%20showing%20hippocampus.jpg
Frontal lobe
Occipital lobe
Cerebellum
Basal ganglia
Hippocampus
Amygdala
PFC
MPFC
Parietal lobe
Temporal lobe
STL
VTL
MTL
Attention
Planning
Imagine/reality discrimination (PCG)
Personality
Judjement
Working Memory
Source monitoring
Retrospective
New info
Prospective
Attention to multiple objects
Working Memory
Motivator
Visual sensory memory
Auditory/verbal memory
Complex visual
Faces
Scenes
(Fusiform gyrus)
(Parahippocampal gyrus)
Long-term declarative memory formation
Spatial representation
Long-term declarative memory formation
Papez circuit
Consolidation
Emotional Memory
Modulator of memory consolidation
Reinforcement learning
Procedural memory encoding (?)
Procedural Memory
Image resource:
http://what-when-how.com/wp-content/uploads/2012/04/tmp3639.jpg
Memory
The ability to store, retain and recall an information.
Memory Encoding
Memory Recall
Memory Maintenance
Sensory
Memory
Short-Term
Memory
Long-Term
Memory
Spike & timing patterns of existing neuronal connections
Chemical gradient
Phosphorylation or dephosphorylation of existing proteins
Changes of synaptic weights
Formation or elimination of synapses
Changes of dendritic spine shape/size
Growth or contraction of arborization
Neurogenesis or elimination of neurons
Sensory
Memory
Short-Term
Memory
Long-Term
Memory
Only degrading (?) due to diffusion of chemicals and activities of ion channels
Selective chunking by attention
Rehearsal
Consolidation, controlled by spike & timing
Synaptic consolidation
System consolidation
Visuo-spatial sketchpad
Phonological loop
LTP
LTD
AMPAR
NMDAR
Na
+
Ca
2+
EPSP
Mg
2+
CamKII
Ca
2+
P
CRE
E-LTP
L-LTP
mGluR
...
1,5
(Gq)
(Gs)
PLC
PKC
MAPK (ERK)
PKA
CREB
cAMP
P
Low frequency
Long exposure
1 Hz
10 -15 min.
(GluR2)
Phosphatases
DAG
2-AG
BDNF
AMPA
PKM zeta
Search of Memory Trace
External
Retrieval
Reconsolidation
Formation of Neural plate
Neurulation
Differentiation
Migration
Survival
Synaptogenesis
0
10
20
30
40
50
60
Years
after birth
Piaget
Erikson
Freud
Formal operational
Sensorimotor
Preoperational
Concrete operational
Care
Hopes
Purpose
Competence
Will
Fidelity
Love
Wisdom
Genital
Oral
Phallic
Anal
Latency
Neurotransmitters
Critical Periods
Months
after birth
0
2
4
6
Motor
Fine Motor
Visual
Auditory
Language
Dentate gyrus (?)
(2-3 wk)
Mathematics
Cognition
3 Weeks after gestation.
Formation of neural tube
4 Weeks after gestation.
Developed from neuroepithelial cells
BMP-4
Notochord
Chordin
Noggin
Follistatin
Skin
Prosencephalon
Mesencephalon
Rhombencephalon
Alar plate
Basal plate
Telencephalon
Cerebrum
Optic
Diencephalon
Thalamus
Hypothalamus
Midbrain
Hindbrain
Rostro-caudal control
Dorso-ventral control
RA
FGF
Shh
BMP
TGF
Chordin
Noggin
Follistatin
Motor
Interneuron
Sensory
+Epidermal
BMP
SVZ
Pia
Cajal-Retzius
cell
Reelin
Vertical
migration
Radial glial
cells
Tangential migration
Tanascin R
LIFR
Trk
CNTF
GDNF1R
CREB
BDNF
NT
3,4
GDNF
Akt
PKC
MAPK
JAK
STAT
SOS
Grb2
PLC
Smad
Samuels B.A. et al., 2007
Pre-synaptic neuron
Post-synaptic neuron
SynCAM
SynCAM
Neurexin
Neuroligin
Glutamate
GABA
DA
2-AG
Gly
ACh
5-HT
NE
Modulators
Mediators
GluR1/3/4
GluR2
Inhibition of
Ca permeability
E-LTP
NR2A/2B
NR1
Postnatal
Adult
LTP
LTD
Excitotoxicity
2+
Ca
2+
Mitochondrial
permeability
Pro-apoptotic genes
expression
AMPAR
NMDAR
Neuron
Astrocyte
Glu
Glu
Gln
Gln
(Mitochondiral)
Glutaminase
Glutamine synthase
AQP4
mGluR
KAR
GABA R
GABA R
A
B
Cl
K
-
+
Hyperpolarization
VTA
SN
Ant.Pit.
NAc
FC
Striatum
Hypoth.
LC
Cortex
Amygdala
Hippocampus
Pons
Cortex
Hippocampus
NBM
Septum
Cortex
Thalamus
Raphe
Cortex
Hippocampus
Striatum
NAc
SCN
Retrograde signaling
Hypothalamus
Pituitary
Adrenal
cortex
Pineal
Gonad
Thyroid
Pancrease
GnRH
Androgen
Progesterone
Estradiol
(E2)
LH
FSH
CRH
Corticotropin
Cortisol
TRH
Thyroxine
TSH
Melatonin
PRL
ADH
Oxt
Insulin
GHRH
GHIH
GH
Antioxidation
Transcription (via ER )
Suppresses inflammation
Attention
Enhance emotional working memory
Trollope A.T. et al., 2012
Fail to consolidate
Facilitate metabolism
Neurogenesis
Myelination
Cytosolic glucose
LTP
Alertness
Motivation
Antioxidation
Facilitate sleep
Lower neuronal excitability (via MT )
1/2
Face, fear, social-related memory
Acute
Chronic
Glucose
Ca
Stress
2+
Homeostatic plasticity
Neuroregeneration
Neuronal Plasticity
Cellular
plasticity
Structural
plasticity
Synaptic
Non-synaptic
Activity-
dependent
Activity-
independent
STM:
LTM:
Chemical profile changes
Last about 7 seconds.
Gene expression profile changes
Last more than 1 minute.
Central to strenghten synaptic connection.
Voltage-gated ion channels
Axon, dendrite and soma
Role in synaptic integration.
Consistent to Hebb's postulate.
LTP
Spike-timing dependent plasticity
LTD
Cells that fire together wire together.
Activity-independent postsynaptic 5-HT -mediated
plasticity represents the cellular mechanism
underlying long-term facilitation
(of AMPA receptors).
Bocchlaro and Feldman, 2004
Synaptic scaling
+
-
Fast & High spike
Slow & Low spike
Phosphorylation
Dephosphorylation
Inwardly rectifying K channel
Kv2.1
+
Kv2.1 opening
Kv2.1 declustering
Factors
Nucleotide polymorphism
Protein aggregates
Abnormal proteosome
Excessive Ca
Programmed Cell Death (PCD)
Autophagy
Necrosis
Apoptosis
Anoikis
Necroptosis
2+
TNF-R1
Apo1
CD95
TNF
Fas
TRADD
DISC
FADD
Nitric oxide
SMAC
IAP
Cyt c
MAC
BAD
BAX
BAK
BID
Apaf1
Bcl-2
Caspase 8,9
Caspase 3
Neural Prunning
Wadsworth W.G., 2005
Mueller B.K. et al., 2009
Limitations in the CNS
Limited growth factors
Slow removal of dead cells
Neural stem cells
Martino G. et al., 2011
Metaplasticity
Potentiated
Active
Silent
Depressed
Determined by the amount of the integrated AMPAR.
Mental
disorder
Amnesia
Dementia
AD
ASD
CJD
PiD
HD
PD
Cellular
Structural
Cortex
Amyloid plaque
Fibrillary tangles
Factors
APP
Presenilin1,2
APOE4
?
Pre-dementia
Early
Advanced
Moderate
Amnesia
Attention deficit
Difficulties in making plans
Agnosia
Apraxia
Aphasia
STM loss
Paraphasia
LTM loss
Behavior change
Complete language loss
Movement loss
Cellular
Structural
Substantia nigra
Locus coeruleus
Lewy body
Factors
SNCA
PRKN
LRRK2
PINK1
?
Early
Tremor
Muscle tone
Moderate
Movement balance loss
Advanced
Attention deficit
Difficulties in making plans
Reduced cognitive speed
Memory recall defected
Cellular
Structural
Striatum, Subsatantia nigra, caudate, putamen
Huntingtin clumps
Factors
HTT
?
Early
Jerky movement (chorea)
Facial muscles defect
Late
Working memory loss
STM loss
LTM loss
Cellular
Structural
Fronto-temporal cortex, Caudate, Putamen, Locus coeruleus
Pick bodies
Factors
MAPT
?
Early
Speech innert
Passive personality
Advanced
Amnesia
Aphasia
Cellular
Structural
Gray matter
Vacuolization
Gliosis
Factors
PRNP
?
Jerky movement
Ataxia
Amnesia
Behavior change
Hallucination
Cellular
Structural
Frontal, Temporal lobe
Limbic system
Corpus callosum
Overconnectivity
Excessive amount of cells
Social interaction difficulties

Communication difficulties

Repetitive behaviors
Aging
Reduced volume of gray matter and white matter

Reduced number of receptors: D , 5HT , GluR
2
1,2,3
Oxidative stress
Vasculation
Information (?)
Systemic decline
Nervous system decline
Working memory
Short-term memory
Long-term memory
Hormonal imbalance
Morrison M.S. and Baxter M.G., 2012
Neuronal death
Circadian rhythm
Kondratova A.A. and Kondratov A.V., 2012
Adjunctive
Suppressive
Amphetamine
LSD
Nicotine
Inhalants
Ethanol
Cocaine
Marijuana
Opioid
Pre-synaptic neuron
Post-synaptic neuron
VMAT2
DAT
MAO
PKC
TH
1
2
3
4
5
D
2
Striatum
Nucleus accumbens
Hippocampus
MAT
DAT
SERT
NET
Methamphetamine
High lipophillicity
MDMA
High effects on 5-HT
Chronic effects
Acute effects
Attention
Wakefulness
Self confident
Aggression
Anxiety
Oxidative stress
Excitotoxicity
Low dose
High dose
DA R
nAChR
Attention
Memory
Euphoria
5-HT R
Opiod R
Sedation
MAO
Herman (tobacco)
DA R
5-HT R
Glu R
Decision making
Confusion
: Structurally similar to endorphins
Analgesic
Dependence
Sedation
Morphine
Heroin
High lipophillicity
Codeine
High bioavailability
AChE
Antioxidation
Antidepressant
Relaxation
CB
1
DAT
SET
NET
Na channels
+
Euphoria
N O
2
Toluene
NMDAR
A
GABA
Analgesic
Anxiolytic
Anesthetic
NMDAR
A
GABA
inhibition
Low dose
Confusion
Anterograde amnesia
High dose
Chronic
Hallucination
Excitotoxicity
Effects to sleep
Hour
0 - 4
Hour
5 - 8
Reduced REM
Increased SWS
Increased REM
Memory booster
Memory alteration
Medicines against amnesia
Inhibition of AChE
Glu signal-to-noise ratio
Donepezil
Tacrine
Galantamine
Rivastigmine
Memantine
Huperzine A (AZ-1)
Drugs
Food
Amphetamine
Nicotine
THC
Thiamine (B1)
Niacin (B3)
Retinol, carotene (A)
Folate (B9), Cobalamin (B12)
Glucose
PUFA
Cholesterol
Zinc
Choline
Flavonoids
Melatonin
Glutathione

Creatine
Coenzyme Q10
Vipocetine
Basic functions
Neuroprotection
Sleep
Exercise
Aerobic physical exercise
BDNF
TrkB
IGF1
Endorphins
Cardiovascular system
Cognitive training
Mental exercise
Crossword, chess
Music playing
Use of non-dominant hand
Multisensory tasks
Active lifestyle
Meditation
The Art of Memory
Repetition
Vision
Ordering
Associating
Chunking
Back-to-First
Affection
Textual
Architectural
Mnemonic
system
Encoding
specificity
Forgetting curve
time
memory
retention
R = e
-t
S
Misinformation
(affection)
Intrusion
error
Schematic
error
Reese-Roediger-McDermott
Imagination
inflation
Source
confusion
Frontal lobe damage
Post-traumatic stress disorder (PTSD)
Treatment
Fluoxetine
Propanolol
SSRI
Beta blocker
Cognitive-behavioral therapy
PKM-zeta blocker (ZIP)
Labile period before reconsolidation
Human brain = 80-120 billion neurons
x 1000-10000 synapses

Representational
theory

Artificial Neural Network
Memory-Prediction framework
Computational
theory
Algorithms
Inputs
Outputs
Neural prosthesis
Sensorimotor
Cognitive
A
B
Input
Output
?
How can memory be augmented?
How is memory recorded?
Step 1
Step 2
Step 3
Compare the patterns of neuronal connection patterns corresponding for different inputs.
Determine the effects of neuronal connection disturbance to memory.
Examine the memory outputs after simulating the neuronal connection without natural inputs.
Akara Metasuk
Committees
Assoc. Prof. Banthit Chetsawang
Prof. Piyarat Govitrapong
Assoc. Prof. Wipawan Thangnipon
Asst. Prof. Nuanchan Chatubhakdikul
Ph.D. MD. Narawut Pakaprot
External information
Internal Neural Codes
Chemical gradient
Cellular structure
Multi-trace Distributed Model
Neural Network Model
Search of
Memory Trace
Retrieval
Image source: http://manmonster.m.a.pic.centerblog.net/o/fb0ffa70.jpg
Full transcript