Selective increase of correlated activity in Arc-positive neurons after chemically induced long-term potentiation in cultured hippocampal neurons

ABSTRACTNew tools in optogenetics and molecular biology have culminated in recent studies which mark immediate-early gene (IEG)-expressing neurons as memory traces or engrams. Although the activity-dependent expression of IEGs has been successfully utilised to label memory traces, their roles in engram specification is incompletely understood. Outstanding questions remain as to whether expression of IEGs can interplay with network properties such as functional connectivity and also if neurons expressing different IEGs are functionally distinct. We investigated the expression of Arc and c-Fos, two commonly utilised IEGs in memory engram specification, in cultured hippocampal neurons. After pharmacological induction of long-term potentiation (LTP) in the network, we noted an emergent network property of refinement in functional connectivity between neurons, characterized by a global down-regulation of network connectivity, together with strengthening of specific connections. Subsequently, we show that Arc expression correlates with the effects of network refinement, with Arc-positive neurons being selectively strengthened. Arc positive neurons were also found to be located in closer physical proximity to each other in the network. While the expression pattern of IEGs c-Fos and Arc strongly overlaps, Arc was more selectively expressed than c-Fos. These IEGs also act together in coding information about connection strength pruning. These results demonstrate important links between IEG expression and network connectivity, which serve to bridge the gap between cellular correlates and network effects in learning and memory.

Get full-text (via PubEx)

Microtubule‐associated protein 2 mediates induction of long‐term potentiation in hippocampal neurons

The FASEB Journal ◽

10.1096/fj.201902122rr ◽

2020 ◽

Vol 34 (5) ◽

pp. 6965-6983 ◽

Cited By ~ 3

Author(s):

Yoonju Kim ◽

You‐Na Jang ◽

Ji‐Young Kim ◽

Nari Kim ◽

Seulgi Noh ◽

...

Keyword(s):

Hippocampal Neurons ◽

Long Term Potentiation ◽

Term Potentiation

Get full-text (via PubEx)

Chemical LTD, but not LTP, induces transient accumulation of gelsolin in dendritic spines

Biological Chemistry ◽

10.1515/hsz-2019-0110 ◽

2019 ◽

Vol 400 (9) ◽

pp. 1129-1139 ◽

Cited By ~ 2

Author(s):

Iryna Hlushchenko ◽

Pirta Hotulainen

Keyword(s):

Synaptic Plasticity ◽

Dendritic Spines ◽

Hippocampal Neurons ◽

Long Term Potentiation ◽

Excitatory Synapses ◽

Signal Molecule ◽

Brain Functions ◽

Dendritic Shaft ◽

Term Potentiation

Abstract Synaptic plasticity underlies central brain functions, such as learning. Ca2+ signaling is involved in both strengthening and weakening of synapses, but it is still unclear how one signal molecule can induce two opposite outcomes. By identifying molecules, which can distinguish between signaling leading to weakening or strengthening, we can improve our understanding of how synaptic plasticity is regulated. Here, we tested gelsolin’s response to the induction of chemical long-term potentiation (cLTP) or long-term depression (cLTD) in cultured rat hippocampal neurons. We show that gelsolin relocates from the dendritic shaft to dendritic spines upon cLTD induction while it did not show any relocalization upon cLTP induction. Dendritic spines are small actin-rich protrusions on dendrites, where LTD/LTP-responsive excitatory synapses are located. We propose that the LTD-induced modest – but relatively long-lasting – elevation of Ca2+ concentration increases the affinity of gelsolin to F-actin. As F-actin is enriched in dendritic spines, it is probable that increased affinity to F-actin induces the relocalization of gelsolin.

Get full-text (via PubEx)

Reexamination of the effects of MCPG on hippocampal LTP, LTD, and depotentiation

Journal of Neurophysiology ◽

10.1152/jn.1995.74.3.1075 ◽

1995 ◽

Vol 74 (3) ◽

pp. 1075-1082 ◽

Cited By ~ 150

Author(s):

D. K. Selig ◽

H. K. Lee ◽

M. F. Bear ◽

R. C. Malenka

Keyword(s):

Hippocampal Neurons ◽

Metabotropic Glutamate Receptor ◽

Low Frequency ◽

Extracellular Recording ◽

Pyramidal Cells ◽

Long Term Potentiation ◽

Metabotropic Glutamate ◽

Term Potentiation ◽

Frequency Stimulation

1. We examined the effects of the metabotropic glutamate receptor (mGluR) antagonist alpha-methyl-4-carboxyphenylglycine (MCPG) on the induction of long-term potentiation (LTP) long-term depression (LTD), and depotentiation in CA1 hippocampal neurons using extracellular recording techniques. 2. MCPG (500 microM) strongly antagonized the presynaptic inhibitory action of the mGluR agonist 1-aminocyclopentane-(1S,3R)-dicarboxylic acid yet failed to block LTP induced with either tetanic stimulation (100 Hz, 1 s) or theta-burst stimulation. 3. To test the possibility that our failure to block LTP was due to prior activation of a "molecular switch" that in its "on" state obviates the need for mGluR activation to generate LTP, we gave repeated periods of prolonged low-frequency stimulation (LFS; 1 Hz, 10 min), a manipulation reported to turn the switch "off." Although this stimulation saturated LTD, subsequent application of MCPG still failed to block LTP. 4. MCPG did not block LFS-induced depotentiation in older slices (4-6 wk) or LFS-induced LTD in older, young (11-18 days), or neonatal (3-7 days) slices. 5. These results demonstrate that MCPG-sensitive mGluRs are not necessary for the induction of LTP, LTD, or depotentiation in hippocampal CA1 pyramidal cells. The possibility remains, however, that their activation may modify the threshold for the induction of these long-term plastic changes.

Get full-text (via PubEx)