Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
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. • • • • 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