Transcript 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
• 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.
• Non-associative “habituation” using the Sea Slug Aplysia
• Pavlovian Fear conditioning in the mice and rats
• Isolated hippocampal slice from rats for Long-term potentiation
• Pavlovian Eye-Blink conditioning in rabbits
Fruit flies and intellectual disability. Bolduc FV, Tully T., Fly (Austin). 2009
Jan–Mar; 3(1): 91–104.
The Sea Slug Aplysia
Synaptic Plasticity Underlying Habituation in Aplysia
Simple Systems: Invertebrate Models of Learning
• Nonassociative Learning in Aplysia (Cont’d)
– Habituation results from presynaptic modification at L7
– Repeated electrical stimulation of a sensory neuron leads to a progressively
smaller EPSP in the postsynaptic motor neuron
Dynamics of dendritic spines in the mouse auditory
cortex during memory formation and memory recall
• Memory consolidation in auditory cortex is necessary for
experience based responses to sounds
• from induction of immediate early genes (IEGs)
• lesions of auditory cortex eliminates the response
• Using green fluorescent protein (GFP) transgenic mice
• In a subset of neurons, primarily in layer 5 of cortex
• Memory formation from auditory-cued fear conditioning
• paired conditioning: increase in spine formation
• unpaired conditioning: spine elimination
• Some new spines persist: a long-lasting trace in the network
• Memory recall triggered by the reexposure of mice to the sound
cue did not lead to changes in spine dynamics.
Synaptic Plasticity Can Be Measured in Simple
Hippocampal Circuits
• Long-term potentiation (LTP)—a stable and enduring increase in
the effectiveness of synapses.
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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.
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.
Hippocampal slice preparation
Hippocampal slice preparation
Hippocampal slice preparation
Hippocampal slice preparation
Hippocampal slice preparation
Roles of the NMDA and AMPA Receptors in the
Induction of LTP in the CA1 Region
Steps in the Neurochemical Cascade
during the Induction of LTP
Common Mechanisms of Synaptic Plasticity Minireview
in Vertebrates and Invertebrates. David L. Glanzman
(2010) Current Biology 20, R31–R36,
Figure 3. General model for learning-related enhancement of excitatory glutamatergic synapses.
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