Remodeling of hippocampal synapses after hippocampus-dependent associative learning

Geinisman, Yuri; Disterhoft, John F.; Gundersen, Hans Jørgen G.; McEchron, Matthew D.; Persina, Inna S.; Power, John M.; Zee, Eddy A. van der; West, Mark J.

doi:10.1002/(sici)1096-9861(20000131)417:1<49::aid-cne4>3.0.co;2-3

Cited by 86 publications

(39 citation statements)

References 55 publications

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“…Second, there may be an increase in the size of climbing fiber-interpositus neuron synapses. Increases in postsynaptic density size occur in the synapses within CA1 stratum radiatum of rabbits trained in trace eyeblink conditioning (Geinisman et al, 2000), which is consistent with the training-related potentiation of the CA1 dendritic field potential (Power, Thompson, Moyer, & Disterhoft, 1997). A third possible structural substrate of increased olivonuclear synaptic efficacy is the proliferation of multiple synapse boutons, which has been reported in the visual cortex (Jones, Klintsova, Kilman, Sirevaag, & Greenough, 1997) and cerebellar cortex (Federmeier, Kleim, & Greenough, 2002) of rats, and in the hippocampus of rabbits (Geinisman, Berry, Disterhoft, Power, & Van der Zee, 2001) after learning.…”

Section: Discussionsupporting

confidence: 73%

Selective Developmental Increase in the Climbing Fiber Input to the Cerebellar Interpositus Nucleus in Rats.

Nicholson

Freeman²

2004

Behavioral Neuroscience

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Previous studies have demonstrated that learning-related cerebellar plasticity and stimulus-elicited neuronal activity emerge ontogenetically in parallel with delay eyeblink conditioning in rats. The present study examined cerebellar interpositus field potentials and multiunit neuronal activity evoked by microstimulation of the inferior olive in Postnatal Day 17 and 24 rats. The slope and amplitude of the excitatory postsynaptic potential and the number of evoked multiunit spikes increased with age, whereas the inhibitory postsynaptic potential caused by Purkinje cell input remained stable. These results are consistent with the notion that the postsynaptic depolarization of cerebellar interpositus neurons caused by cerebellar afferents (e.g., the climbing fibers of the inferior olive) is a critical factor contributing to the ontogeny of delay eyeblink conditioning in rats.

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Section: Discussionsupporting

confidence: 73%

Selective Developmental Increase in the Climbing Fiber Input to the Cerebellar Interpositus Nucleus in Rats.

Nicholson

Freeman²

2004

Behavioral Neuroscience

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“…A stereologic disector technique was used to measure synapse density (West and Gundersen, 1990;Geinisman et al, 2000). Each disector consisted of micrographs of two adjacent ultrathin sections, a reference section and a look-up section immediately above it.…”

Section: Assessment Of Synapse Number By Electron Microscopementioning

confidence: 82%

Spatial relationship between synapse loss and β‐amyloid deposition in Tg2576 mice

Dong

Martin

Chambers

et al. 2006

J of Comparative Neurology

134

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Although there is evidence that β-amyloid impairs synaptic function, the relationship between β-amyloid and synapse loss is not well understood. In this study, we assessed synapse density within the hippocampus and the entorhinal cortex of Tg2576 mice at 6-18 months of age using stereological methods at both the light and electron microscope levels. Under light microscopy, we failed to find overall decreases in the density of synaptophysin-positive boutons in any brain areas selected, but bouton density was significantly decreased within 200 μm of compact β-amyloid plaques in the outer molecular layer of the dentate gyrus and layers II and III of the entorhinal cortex at 15-18 months of age in Tg 2576 mice. Under electron microscopy, we found overall decreases in synapse density in the outer molecular layer of the dentate gyrus at both 6-9 and 15-18 months of age, and in layers II and III of the entorhinal cortex at 15-18 months of age in Tg 2576 mice. However, we did not find overall changes in synapse density in the stratum radiatum of the CA1 subfield. Furthermore, in the two former brain areas, we found a correlation between lower synapse density and greater proximity to β-amyloid plaques. These results provide the first quantitative morphological evidence at the ultrastructure level of a spatial relationship between β-amyloid plaques and synapse loss within the hippocampus and the entorhinal cortex of Tg2576 mice.

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“…For example, contrary to conditioning of the eyeblink response, the development of more complex motor skills involving coordinated limb movements is not associated with changes in synapse number within deep cerebellar nuclei (20). In addition, trace eyeblink conditioning was associated with an increase in the area of synaptic contacts within the hippocampus but not an overall increase in synapse number (31). Thus, memory may be encoded via several mechanisms that coalesce in different ways across multiple brain regions (32).…”

Section: Discussionmentioning

confidence: 99%

Synapse formation is associated with memory storage in the cerebellum

Kleim

Freeman

Bruneau

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

164

124

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The idea that memory is encoded by means of synaptic growth is not new. However, this idea has been difficult to demonstrate in the mammalian brain because of both the complexity of mammalian behavior and the neural circuitry by which it is supported. Here we examine how eyeblink classical conditioning affects synapse number within the cerebellum; the brain region essential for long-term retention of the conditioned response. Results showed eyeblink-conditioned rats to have significantly more synapses per neuron within the cerebellar interpositus nucleus than both explicitly unpaired and untrained controls. Further analysis showed that the increase was caused by the addition of excitatory rather than inhibitory synapses. Thus, development of the conditioned eyeblink response is associated with a strengthening of inputs from precerebellar nuclei rather than from cerebellar cortex. These results demonstrate that the modifications of specific neural pathways by means of synaptogenesis contributes to formation of a specific memory within the mammalian brain.For every act of memory, every exercise of bodily aptitude, every habit, recollection, train of ideas, there is a specific neural grouping, or co-ordination, of sensations and movement, by virtue of specific growths in cell junctions (1).T he neural circuits critical for the acquisition and performance of the conditioned eyeblink response are localized to the cerebellum (2). Information regarding the unconditioned stimulus (US) and conditioned stimulus (CS) converge within both the cerebellar cortex and the interpositus nucleus. CS information is relayed via ponto-cerebellar projections, whereas US information is relayed via the olivo-cerebellar pathway (2, 3). Although the cerebellar cortex is involved in modulating some aspects of the conditioned response (CR) (4, 5), the interpositus nucleus is the critical brain structure supporting long-term retention of the CR (2, 6, 7). Neuronal activity within the interpositus nucleus is highly correlated with development of the CR (5, 7), and inactivation of the interpositus prevents both CR acquisition and performance (8).Although the locus of the memory trace is clear, the cellular mechanisms underlying the formation of the CS͞US association are poorly understood. Several mechanisms have been proposed, including increases in the intrinsic excitability of interpositus neurons and reduced inhibition via depression of Purkinje cell activity (9). The fact that inhibition of specific synaptic enzymes (10) and neurotransmitter receptors (11) within the interpositus nucleus impair learning suggests that changes in synaptic function are involved. Transient changes in enzyme or receptor activity, however, would seem incapable of supporting the long-term encoding of the CS͞US association. Recent work has shown that microinjections of a protein synthesis inhibitor into the interpositus nucleus impairs the acquisition but not the expression of the CR (12). This finding suggests that strengthening of the CS pathway may involve more...

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Remodeling of hippocampal synapses after hippocampus-dependent associative learning

Cited by 86 publications

References 55 publications

Selective Developmental Increase in the Climbing Fiber Input to the Cerebellar Interpositus Nucleus in Rats.

Selective Developmental Increase in the Climbing Fiber Input to the Cerebellar Interpositus Nucleus in Rats.

Spatial relationship between synapse loss and β‐amyloid deposition in Tg2576 mice

Synapse formation is associated with memory storage in the cerebellum

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