scholarly journals Stability of excitatory structural connectivity predicts the probability of CA1 pyramidal neurons to become engram neurons

2019 ◽  
Author(s):  
Tim P. Castello-Waldow ◽  
Ghabiba Weston ◽  
Alireza Chenani ◽  
Yonatan Loewenstein ◽  
Alon Chen ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Structural Connectivity ◽  
Synaptic Connectivity ◽  
Two Photon ◽  
Ca1 Pyramidal Neurons ◽  
Trace Fear Conditioning ◽  
Hippocampal Ca1 ◽  
Trace Fear ◽  
Activity Dependent ◽  
Deep Brain

SUMMARYNeurons undergoing activity-dependent plasticity represent experience and are functional for learning and recall thus they are considered cellular engrams of memory. Although increase in excitability and stability of structural synaptic connectivity have been implicated in the formation and persistance of engrams, the mechanisms bringing engrams into existence are still largely unknown. To investigate this issue, we tracked the dynamics of structural excitatory synaptic connectivity of hippocampal CA1 pyramidal neurons over two weeks using deep-brain two-photon imaging in live mice. We found that neurons that will prospectively become part of an engram display higher stability of connectivity than neurons that will not. A novel experience significantly stabilizes the connectivity of non-engram neurons. Finally, the density and survival of dendritic spines negatively correlates to freezing to the context but not to the tone in a trace fear conditioning learning paradigm.

scholarly journals Hippocampal neurons with stable excitatory connectivity become part of neuronal representations

PLoS Biology ◽  
2020 ◽  
Vol 18 (11) ◽  
pp. e3000928 ◽  
Author(s):  
Tim P. Castello-Waldow ◽  
Ghabiba Weston ◽  
Alessandro F. Ulivi ◽  
Alireza Chenani ◽  
Yonatan Loewenstein ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Time Window ◽  
Structural Connectivity ◽  
Time Lapse ◽  
Early Gene ◽  
Synaptic Connectivity ◽  
Time Duration ◽  
Hippocampal Ca1 ◽  
Cornu Ammonis

Experiences are represented in the brain by patterns of neuronal activity. Ensembles of neurons representing experience undergo activity-dependent plasticity and are important for learning and recall. They are thus considered cellular engrams of memory. Yet, the cellular events that bias neurons to become part of a neuronal representation are largely unknown. In rodents, turnover of structural connectivity has been proposed to underlie the turnover of neuronal representations and also to be a cellular mechanism defining the time duration for which memories are stored in the hippocampus. If these hypotheses are true, structural dynamics of connectivity should be involved in the formation of neuronal representations and concurrently important for learning and recall. To tackle these questions, we used deep-brain 2-photon (2P) time-lapse imaging in transgenic mice in which neurons expressing the Immediate Early Gene (IEG) Arc (activity-regulated cytoskeleton-associated protein) could be permanently labeled during a specific time window. This enabled us to investigate the dynamics of excitatory synaptic connectivity—using dendritic spines as proxies—of hippocampal CA1 (cornu ammonis 1) pyramidal neurons (PNs) becoming part of neuronal representations exploiting Arc as an indicator of being part of neuronal representations. We discovered that neurons that will prospectively express Arc have slower turnover of synaptic connectivity, thus suggesting that synaptic stability prior to experience can bias neurons to become part of representations or possibly engrams. We also found a negative correlation between stability of structural synaptic connectivity and the ability to recall features of a hippocampal-dependent memory, which suggests that faster structural turnover in hippocampal CA1 might be functional for memory.

Protein Kinase C Activation Decreases Activity-Dependent Attenuation of Dendritic Na+ Current in Hippocampal CA1 Pyramidal Neurons

1998 ◽  
Vol 79 (1) ◽  
pp. 491-495 ◽  
Author(s):  
Costa M. Colbert ◽  
Daniel Johnston
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Action Potentials ◽  
Pyramidal Neurons ◽  
Phorbol Esters ◽  
Ca1 Pyramidal Neurons ◽  
Kinase C ◽  
Hippocampal Ca1 ◽  
Activity Dependence ◽  
Activity Dependent

Colbert, Costa M. and Daniel Johnston. Protein kinase C activation decreases activity-dependent attenuation of dendritic Na+ current in hippocampal CA1 pyramidal neurons. J. Neurophysiol. 79: 491–495, 1998. Action potentials recorded from the soma of CA1 pyramidal neurons remain relatively uniform in amplitude during repetitive firing. In contrast, the amplitudes of back-propagating action potentials in dendrites decrease progressively during a spike train. This activity-dependent decrease in amplitude is dependent on the frequency of firing during the train and distance from the soma. Previously, we described a property of Na+ channels that provides a plausible mechanism for the activity dependence of the amplitude of the dendritic action potentials: available Na+ current decreases during trains of action potentials through an inactivation, distinct from fast inactivation, that appears rapid in onset, but slow and voltage-dependent in its recovery. In this study we found that activation of protein kinase C by phorbol esters decreased this activity-dependent inactivation of pharmacologically isolated Na+ current in cell-attached dendritic, but not somatic, patches. Similarly in whole cell recordings phorbol esters decreased the attenuation of back-propagating dendritic action potentials during trains. These results indicate a novel effect of protein kinase C on the dendritic Na+ channel and further support the hypothesis that the activity dependence of the dendritic action potentials is derived from the inactivation properties of Na+ channels.

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