Overview and Integration
Behavioral, Cognitive, and Clinical Neuroscience
Place Cells
PET Techniques
Normal Brain AD Brain
Neuroscience from Historical and
Biographical Perspectives
Brain Hypothesis
Neuron Hypothesis
For a history of neuroscienece timeline: neurolab.jsc.nasa.gov/timeline.htm
Site of Thinking: Heart, Ventricles,
Brain
Phrenology and Localization of
Function
Neurons as Units or a Neural Net
Jan Purkinje
Purkinje cell – first viewed in 1837
Cajal and Golgi – 1906 Nobel
Prize in Physiology
Santiago Ramon y Cajal
Camillo Golgi
Sherrington and the “Synapse”
1932 Nobel Prize in Physiology
Lashley’s Search for the Engram
in the 1920s
After training, cortical lesions are made.
Three different lesion locations are shown
in red, blue, and yellow
Rats are trained to run through a
maze without entering blind alleys.
Errors are
associated
with the
size rather
than the
locus of the
lesion.
Donald Hebb and the Cell Assembly
1949
20th and 21st Century Advances
Electrophysiology
Imaging
EEG
Genetics
CT Scan
Human genome
MRI
Mouse genome
Multiple Unit Recording
PET
Clinical genotyping
Single Unit Recording
SPECT
Transgenic animals
Tetrode Recording
fMRI
Knock-out animals
ERPs
MEG
Comparative Neuroscience: Parallels in BrainBehavior Relationships Across Species
Spatial Location
Activation maps of 2 CA1 hippocampal
place cells
Fear Conditioning
Associative Learning
Eyeblink Classical Conditioning: Behavioral Parallels
in All Mammals Including Humans
Conditioned Stimulus (CS)–Unconditioned Stimulus (US) Pairings =
Conditioned Response (CR)
Genetics, Neurobiology, and Behavior
Spatial and Temporal Control of
Transgene Expression
Doubly Transgenic Mice
Region Specific Promoter
+
tTA responsive Promoter
tTA-Gene
_
Effector Gene
Microarrays Method of examining changes in gene
expression associated with event, drug, or disease
Polymerase Chain Reaction
Human Genotyping: Alipoprotein E
Anatomical and Functional Neuroanatomy
Tutorial: www.neuropat.dote.hu
Sulci and Gyri in the Human Brain
Ventral View of MTL
Human Limbic System
Individual Differences in Brains
Neurons, Membranes, and
Electrical Potentials
Neuronal Membrane
Ion Concentration Gradients
Summation of EPSPs and IPSPs
Ion Flow in 5 Phases of the Action Potential
Synaptic Transmission and Brain
Neurochemistry
Transmission at the Synapse
Brain Neurotransmitter Pathways
Drug Effects on Neurotransmission
Consciousness and Sleep
EEG Stages in
Wakefulness
and Sleep
Cortical Functions and Their
Measurement: Vision as a Prototype
Receptive Fields
Dorsal (“Where”) and Ventral (“What”)
Visual Streams in Human (PET)
Dorsal (where) pathway
shown in green and blue
and Ventral (what)
pathway shown in yellow
and red serve different
functions. (Courtesy of
Leslie Ungerleider).
Visual Attention:
Color, Form, and Movement
Activation remaining
after divided condition
subtracted from each
of 3 focal attention
conditions. Red boxes
= color activation.
Yellow boxes = motion
activation. (Courtesy of
Posner and Raichle).
Developmental Neuroscience
Halo response of an
embryonic chick
ganglion after
incubation with nerve
growth factor. (Courtesy
of Rita Levi-Montalcini)
Photographs of Human
Fetal Brain Development
Lateral view of the human
brain shown at one-third size
at several stages of fetal
development. Note the
gradual emergence of gyri
and sulci.
Eight Phases in Embryonic and Fetal
Development at a Cellular Level
1. Mitosis/Proliferation
2. Migration
3. Differentiation
4. Aggregation
5. Synaptogenesis
6. Neuron Death
7. Synapse Rearrangement
8. Myelination
8 stages are sequential
for a given neuron, but
all are occurring
simultaneously
throughout fetal
development
Recovery from Aphasia: Imaging
Neural Correlates
Metabolic correlates
of recovery in 2
patients.
Perilesional regions
near damaged left
inferior frontal gyrus
identified by single
subject fMRI
analysis.
Rosen et al. (2000) Neurology, 55,1883-1894.
Behavioral Remediation for Dyslexia:
Imaging Brain Outcomes
Phonological training in
dyslexics who have little
or no activation in left
neocortical regions
activated during reading in
normal children results in
increased activation in
critical regions on the left
AND increased activation
in homologous right
neocortex.
Temple et al. (2003) PNAS, 100, 2860-2865.
Emotion: Normal and Abnormal
Papez Circuit (1937)
Orbital Frontal Cortex and Impaired
Social and Sexual Behavior
After an on-the-job explosion blew a 13-pound tamping rod
straight through Gage's head, the well-liked construction
foreman remained conscious. He was able to talk and even
walked to the cart that took him to Cavendish, Vermont where he
was treated by Dr. John Martyn Harlow.
Hypofunctionality and/or Lesions of
Orbitofrontal Cortex Affect Emotion
Fear Conditioning: Parallel Circuits in
Humans and Rodents
Neurobiology of Memory, Memory
Impairment, and Dementia
Normal Brain
AD Brain
Long Term Potentiation
Formation of New Synapses
Between Neurons Showing LTP
Electron microscopic examination
of synapses before and after
undergoing LTP. Hippocampal
neurons showing increases in Ca2+
also showed doubling of spines
(From Toni et al., 1999).
Synaptic Changes that Could
Support Memory
Forms of Long Term Memory
Declarative
•Semantic
•Episodic
Nondeclarative
•Nonassociative (sensitization
and habituation)
•Procedural (Skill learning)
•Priming
•Simple Classical Conditioning
Language and Executive Function
Executive Function: Eclectic or Unified?
In addition to Attention and Working Memory
•Generating Ideas
•Initiating
•Inhibiting
•Planning
•Setting Goals
•Regulating and Verifying
•Temporally Ordering
Dysfunction in Orbitofrontal Cortex
Pseudodepression
Pseudopsychopathy
•Outward apathy and indifference
•Immature behavior
•Loss of initiative
•Lack of tact and restraint
•Reduced sexual interest
•Coarse language
•Little overt emotion
•Promiscuous sexual
behavior
•Little or no verbal output
•Increased motor
activity
•General lack of social
graces
Movement and Movement
Selection
Speech as an Example of Movement
Selection
PET Image of Speaking a Heard Word
The Wernicke-Geschwind Model
Norman Geschwind (1974) reintroduced Wernicke's language
circuit in the mid-twentieth century, and the WernickeGeschwind model of brain and language function is still the
basis for contemporary understanding
The Wernicke-Geschwind Model
is an Oversimplification
Binder (2003) pointed out that the supramarginal gyrus along with the
posterior superior temporal gyrus (including the planum temporale) and
the posterior insula play a critical role in the selection and production
of ordered phoneme sequences.
Individual Variation in Lesion Sites of Broca’s,
Wernicke’s, Conduction, and Global Aphasia
Composite radioisotope
brain scan for patients
with each type of
aphasia. Darker regions
indicate areas where the
lesions of many
individual patients
overlap. The isotope
scans operate on the
principle that the labeled
compound can cross the
blood-brain barrier in
damaged tissue but not in
healthy cortical regions.
Dyslexia: Disruption in Posterior
Brain Regions
Neural systems for reading that are disrupted in dyslexic children.
Shaywitz et al. (2002) Biol. Psychiat., 52, 101-110.
Plasticity in Dyslexia as Well as
Stroke
Temple et al. (2003) PNAS, 100,
2860-2865.
Rosen et al. (2000) Neurology,
55,1883-1894.