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 or 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

Dynamics of dendritic spines in the mouse auditorycortex 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.• 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