Download neural plasticity

Neural Mechanisms of Memory Storage
• Molecular, synaptic, and cellular events store
information in the nervous system.
• New learning and memory formation can involve
• new neurons
• new synapses
• changes in synapses in response to biochemical signals
• increased neurotransmitter release
• changes in neurotransmitter-receptor interactions.
• Neuroplasticity (or neural plasticity) is the ability of
neurons and neural circuits to be remodeled by
experience while interacting with the environment.
Synaptic Changes That May Store Memories
Memory Storage Requires Neuronal Remodeling
Lab animals living in a complex environment demonstrated
biochemical and anatomical brain changes from those
living in simpler environments.
Three housing conditions:
– Standard condition (SC)
– Impoverished (or isolated) condition (IC)
– Enriched condition (EC)
Animals housed in EC, compared to those in IC, developed:
– heavier, thicker cortex;
– enhanced cholinergic activity;
– More dendritic branches (especially on basal dendrites near the cell body),
with more dendritic spines suggesting more synapses.
Experimental Environments to Test the Effects of
Enrichment on Learning and Brain Measures
Measurement of Dendritic Branching
Several animal models have been used in the
study of memory and cognition
• Non-associative “habituation” using the Sea Slug Aplysia
• Pavlovian Fear conditioning in the mice and rats
• Pavlovian Eye-Blink conditioning in rabbits
• Pavlovian olfactory conditioning in Drosophila
• to understand the molecular genetic basis of learning and memory
• Cognitive deficits in fly mutants involving genes similar to those related to
human intellectual disability (Androschuk 2015).
• From Learning to Memory: What Flies Can Tell Us about Intellectual
Disability Treatment. Androschuk A, Al-Jabri B, Bolduc FV. Front
Psychiatry. 2015 Jun 3;6:85.
• Isolated hippocampal slice from rats for Long-term potentiation
Synaptic Plasticity Underlying Habituation in Aplysia
The hippocampus
• The hippocampus is a 3 layer cortex with two main subdivisions:
– dentate gyrus (DG)
– cornu ammonis (CA). with 2 regions: CA1 and CA3.
• the subiculum and entorhinal cortex connect the hippocampus to the
neocortex
• Bilateral hippocampal damage will impair remembering faces and
other declarative memory
• But are
–
–
–
–
motor task such as mirror drawing
sensory-motor learning
delayed non-match to sample task (DNMS)
radial spatial maze
The hippocampus: schematic connections
Plasticity:
1. Perforant pathway:
postsynaptic LTP and LTD
(NMDA-R dependent)..
2. Mossy fibers: presynaptic
LTP (NOT NMDA-R).
3. Schaffer collaterals:
postsynaptic LTP and LTP
(NMDA-R dependent).
This diagram illustrates the famous trisynaptic pathway. Fibers from the entorhinal cortex reach
the DG via the perforant path and contact the DG granule cell dendritic spines. The DG granule
cells then project mossy fibers to the proximal apical dendritic spines of CA3 pyramidal cells. The
CA3 pyramidal cells then project (Schaffer collaterals) to the CA3 apical dendritic spines. CA3
pyramids the project out of the hippocampus.
Also shown is the projection of CA3 pyramidal cells down to the hypothalamus (mamillary body)
via the fornix (this pathway is both input and output).
Damage To The Hippocampus
• Famous case of Henry Molaison (H.M.)
– Although much more then hippocampus was damaged
– Anterograde declarative amnesia
– Could learn new nondeclarative such as motor skills
• although it took H.M. more practice
• Individuals with hippocampal damage have a variety of impairments
– Unable to learn from feedback if it is delayed by even six seconds
– Unable to recall how to grasp new tools
– Poor consolidation of complex visual scenes where objects overlap and occlude
each other
– Trouble identifying odd scenes, such as a large bird skating on the beach
– Lack of detail when asked to picture themselves in a certain place such as
“Imagine you are lying on a white sandy beach in a beautiful tropical bay,”
– Can not consolidate spatial information “ where are the keys?”
What Does The Hippocampus Do?
• Consolidation of short-term into long-term memory
– Declarative (sematic and episodic) and Spatial
– rapid changes in hippocampal synaptic connections that last for hours to days
– transfers new memories to neocortex over a period of days to weeks
• The latter process might involve memory replay during sleep
– important for memory retrieval producing “reconsolidation”
• Bind together new information and integrate it with that which we
have already learned.
• Connect information about individual items recorded in memory
with new contexts.
Long-Term Potentiation Occurs in the Hippocampus
Synaptic Plasticity Can Be Measured in Simple
Hippocampal Circuits
• LTP occurs at several sites in the hippocampal formation—formed
by the hippocampus, the dentate gyrus and the subiculum (also
called subicular complex or hippocampal gyrus).
• The hippocampus has regions called CA1, CA2, and CA3
(CA=Cornus Ammon which means Ammon’s Horn).
• The CA1 region has two kinds of glutamate receptors:
• NMDA receptors (after its selective ligand, N-methyl-D-aspartate)
• AMPA receptors (which bind the glutamate agonist AMPA)
• Glutamate first activates AMPA receptors.
• NMDA receptors do not respond until enough AMPA receptors are
stimulated, and the neuron is partially depolarized.
Roles of the NMDA and AMPA Receptors in the
Induction of LTP in the CA1 Region
Synaptic Plasticity Can Be Measured in Simple
Hippocampal Circuits
• Long-term potentiation (LTP)—a stable and enduring increase in
the effectiveness of synapses.
•
•
•
•
Synapses in LTP behave like Hebbian synapses:
Tetanus drives repeated firing.
Postsynaptic targets fire repeatedly due to the stimulation.
Synapses are stronger than before
• LTP can be generated in
• conscious and freely behaving animals
• in anesthetized animals
• in tissue slices
• LTP is evident in a variety of invertebrate and vertebrate species.
• LTP can also last for weeks or more.
• Superficially, LTP appears to have the hallmarks of a cellular
mechanism of memory.
Steps in the Neurochemical Cascade
during the Induction of LTP
In the Adult Brain, Newly Born
Neurons May Aid Learning
• Neurogenesis, or birth of new neurons, occurs mainly in the dentate
gyrus in adult mammals.
• Neurogenesis and neuronal survival can be enhanced by
• Exercise
• environmental enrichment
• memory tasks
• neurogenesis occurs in hippocampus-dependent learning.
• Conditional knockout mice, with neurogenesis selectively turned off in
specific tissues in adults, showed impaired spatial learning but were otherwise
normal.
• Genetic manipulations can increase the survival of newly generated neurons in
the dentate, resulting in improved performance.
• These animals showed enhanced hippocampal LTP, which was expected since
younger neurons display greater synaptic plasticity.
Neurogenesis in the Dentate Gyrus