Neocortical Activation by Electrical and Chemical Stimulation of the Rat Inferior Colliculus: Intrac

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Plasticity How plastic is the brain? -Most
tissues and organs show a high degree of
plasticity, i.e., the ability to change over
time and re-grow after damage or injury. -In
contrast, it has been a long-standing observation
that recovery after brain damage is often very
poor, indicating that the brain has only very
limited capacity to show re-generation and
plasticity. -Similarly, most functions carried
out by the central nervous system (CNS) remain
highly consistent, especially after the initial
development of the CNS (e.g., basic perceptual
and motor functions, but also complex behavior,
personality characteristics, etc.) gt Thus, it
appears that the adult CNS is characterized by a
great deal of stability and inflexibility. Early
neuroscientists were skeptical regarding the
ability of the adult CNS to show plasticity.
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Ioan Minea (1878-1941) -coined term neuronal
plasticity -performed tissue transplants
(nerves, ganglia, skin, etc.) and observed
metamorphic (changes in appearance) processes
of of the transplanted tissue (e.g., degeneration
of tissue, but also survival and growth of tissue
including nerves sprouting) -early work was
limited to peripheral nerves it was assumed that
the CNS does not allow for plastic phenomena that
can be seen in the peripheral nervous system and
other body tissues
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Santiago Ramon y Cajal (1852-1934)
neuroanatomist and founder of modern
neuroscience research -formulated Neuron
Doctrine (nervous system composed of individual
cells/neurons) -discovered dendritic
spines -awarded 1906 Nobel prize with C. Golgi
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-Ambiguity is justified (limited plasticity after
CNS insults)
TINS 25589 (2002)
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Cajals ambiguity regarding Plasticity prolife
rative inability (after development)...growth
and regeneration of axons and dendrites dried
up irrevocably restorative plasticity,
i.e., some limited capacity for plastic
reorganization and sprouting as a mechanism to
allow compensation after brain injury
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D. O. Hebb (1904-1985)
Examined influence of environment and on behavior
and intelligence in rats Brains are shaped by
experience, i.e., they are plastic
The Organization of Behavior (1949) -in
this book and lectures given in the years prior
to its publication, Hebb formulated the first
conceptual framework of how neurons alter
(strengthen or weaken) their connectivity -Hebb
speculated that correlated neural activity
strengthens synaptic connections, (i.e.,
neurons fire together wire together), whereas
random, unrelated activity patterns in a group of
neurons results in weakened connections among
these cells (i.e., you lose your link when you
are out of synch) -functionally related,
strongly connected neurons form cell assemblies
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Hebbs original drawing of a cell assembly in
the primary visual cortex
synapse weakened
Light
synapse strengthened
Neurons A, B C are active together gt
connections between ABC are strengthened
Neurons A/D E are not active together gt
connections between DE are weakened
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Theoretical mechanisms of synaptic plasticity
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Experimental Support for Brain Plasticity
Two experimental approaches in the 1960s to
demonstrate experience-dependent brain
plasticity a. Environmental housing -gt effects
on cortex Berkeley group (Bennett, Diamond,
Rosenzweig, others) b. Visual deprivation
-gt effects on visual cortex development
Hubel and Wiesel
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Environmental Enrichment
Berkeley group -initially studied correlation
between markers for acetylcholine (ACh, the
enzyme acetylcholinesterase, AChE) and problem
solving in rats -subsequently examined the
effects of training on AChE levels -then started
to study the effects of different housing
environments on AChE levels a impoverished
rearing b social rearing c enriched rearing
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Brain Structure Rearing AChE Levels
(1960) EC gt IC Cortex Thickness EC gt
IC Weight (1962) Callosum Thickness EC gt
IC Axon Number Neuron Size EC gt
IC Dendrite Branching EC gt IC Spine
Density Synapses/Neuron EC gt IC Glial Cell
Processes EC gt IC Cerebral Vasculature EC gt
IC Mitochondria size EC gt IC Adult
Neurogenesis EC gt IC Cognitive Capacity EC
gt IC EC enriched condition IC
impoverished condition
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Comery, Shah, Greenough, NLM 63271 (1995)
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T. Hubel and D. Wiesel Role of Experience in
Visual Cortex Development
-Nobel Prize in 1981 -Hubel and Wiesel
characterized the organization of the primary
visual cortex (V1, e.g., ocular dominance
columns) and described functional response
properties of V1 neurons (line
detectors) -also studied developmental
plasticity of V1 and examined how visual input
and experience (and the absence thereof) affect
the developmental maturation of V1
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Ocular Dominance Columns Hard-Wired or
Experience-Dependent?
Ocular dominance columns -form early in life
when inputs from left and right eye
segregate into discreet terminal fields in the
cortex -this leads to systematically alternating
strips of cortex that receive in put from one
eye (i.e., left-right-left-right-etc.) Hubel and
Wiesel covered one eye during early postnatal
development monocular deprivation
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Monocular Deprivation
Normal Cortex (both eyes open)
Both eyes represented
Deprived Cortex (one eye closed)
One eye represented
gtThe lack of input/stimulation of one eye leads
to the disappearance of the cortical
representation of that eye
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Critical Period Macaque Monocular Deprivation
gt these effects occur early in life, during a
so-called critical/sensitive period
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Hubel and Wiesels work shows that
the -development of visual system
requires appropriate sensory stimulation -the
organization of the visual cortex changes with
different sensory experience gt environmental
and experience-dependent factors interact with
genetic programs to determine structure and
functions of the nervous system
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Mechanisms of Synaptic Plasticity Long-Term
Potentiation (LTP)
-Bliss and Lomo (1973) discovered LTP, a
synaptic plasticity mechanism -stimulate input
fibers (perforant path) to hippocampus and
recorded post- synaptic response of hippocampal
Neurons to the stimulation -a short episode of
high-frequency Stimulation resulted in a
pronounced, Long-lasting increase in the
post- synaptic response
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-high-frequency stimulation -gt concurrent pre-
and postsynaptic activity -results in
intracellular changes that increase synaptic
strength (e.g., more receptors, sprouting of new
dendritic spines and axon terminals) -direct
support for Hebbs hypothesis that synchronized
activity of cells leads to increased coupling
among them
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Bliss and Lomo (1973) Long-term
potentiation LTP shares many features with
memory encoding -rapid induction (lt 1
s) -variable duration (minutes, hours, days,
weeks, months) -can be very long-lasting (gt 1
year in rats) gt Offers a model to study the
synaptic, cellular, and molecular basis of
neural plasticity and memory formation
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Plasticity in Simple Nervous Systems
Eric Kandel Nobel Prize (2000) -studied learning
and plasticity in the sea slug Aplysia (20,000
central neurons) -simple system allows a more
direct assessment of behavior/learning/memory
storage to changes in nervous system
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Aplysia shows many types of learning and
memory also seen in complex mammals A.
Habituation B. Sensitization C. Classical
Conditioning Short-term Memory Long-term Memory
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Sensitization in Aplysia
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Synaptic and Cellular Learning Mechanisms
-detailed mapping of sensory neurons (touch,
shock) and motor neurons (gill movements) allows
assessment of synaptic changes that mediate
changes in withdrawal reflex
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Molecular and Genetic Learning Mechanisms
-in addition, a cascade of intracellular
mechanisms (2nd messengers, signals to nucleus,
gene transcription and translation, new proteins)
has been identified that occur during learning in
Aplysia
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Summary 1. Initial doubts regarding the
ability of the adult, intact nervous system to
show plastic changes (early 1900s) 2. Hebb
establishes theoretical basis for
experience- dependent changes in synaptic
connectivity (1930-40s) 3. First empirical
support for experience-dependent brain plasticity
(1960s) 4. Characterization of the first
cellular and synaptic model of brain plasticity
(1970s) 5. Detailed analyses of cellular,
molecular, and genetic mechanisms mediating brain
plasticity (1980s-present)