Reversing Aging: Decline in Complex Olfactory Learning Can be Rectified by Restoring Intrinsic Plasticity of Hippocampal CA1 Pyramidal Neurons

Awasthi, Richa; Yuan, Qi; Barkai, Edi

doi:10.1002/adbi.202300323

Cited by 2 publications

(1 citation statement)

References 40 publications

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“…The long-term storage of the olfactory information in the PC may, therefore, be favored by the KAR-mediated suppression of I sAHP . However, the odor learning-induced suppression of I sAHP is impaired in PC pyramidal neurons from old mice, suggesting that GluK2 may represent a promising target to alleviate cognitive decline during aging [145]. Taken together, these preliminary findings strongly suggest that flux-independent signaling by KARs is more prone to induce LTP rather than LTD.…”

Section: Flux-independent Signaling By Kars Regulates Axon Growth And...mentioning

confidence: 80%

Two Signaling Modes Are Better than One: Flux-Independent Signaling by Ionotropic Glutamate Receptors Is Coming of Age

Brunetti,

Soda,

Berra-Romani

et al. 2024

Biomedicines

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Glutamate is the major excitatory neurotransmitter in the central nervous system. Glutamatergic transmission can be mediated by ionotropic glutamate receptors (iGluRs), which mediate rapid synaptic depolarization that can be associated with Ca2+ entry and activity-dependent change in the strength of synaptic transmission, as well as by metabotropic glutamate receptors (mGluRs), which mediate slower postsynaptic responses through the recruitment of second messenger systems. A wealth of evidence reported over the last three decades has shown that this dogmatic subdivision between iGluRs and mGluRs may not reflect the actual physiological signaling mode of the iGluRs, i.e., α-amino-3-hydroxy-5-methyl-4-isoxasolepropionic acid (AMPA) receptors (AMPAR), kainate receptors (KARs), and N-methyl-D-aspartate (NMDA) receptors (NMDARs). Herein, we review the evidence available supporting the notion that the canonical iGluRs can recruit flux-independent signaling pathways not only in neurons, but also in brain astrocytes and cerebrovascular endothelial cells. Understanding the signaling versatility of iGluRs can exert a profound impact on our understanding of glutamatergic synapses. Furthermore, it may shed light on novel neuroprotective strategies against brain disorders.

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Section: Flux-independent Signaling By Kars Regulates Axon Growth And...mentioning

confidence: 80%

Two Signaling Modes Are Better than One: Flux-Independent Signaling by Ionotropic Glutamate Receptors Is Coming of Age

Brunetti,

Soda,

Berra-Romani

et al. 2024

Biomedicines

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Learning‐induced bidirectional enhancement of inhibitory synaptic metaplasticity

Kundu,

Paul,

Reuevni

et al. 2024

The Journal of Physiology

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Training rodents in a particularly difficult olfactory‐discrimination (OD) task results in the acquisition of the ability to perform the task well, termed ‘rule learning’. In addition to enhanced intrinsic excitability and synaptic excitation in piriform cortex pyramidal neurons, rule learning results in increased synaptic inhibition across the whole cortical network to the point where it precisely maintains the balance between inhibition and excitation. The mechanism underlying such precise inhibitory enhancement remains to be explored. Here, we use brain slices from transgenic mice (VGAT‐ChR2‐EYFP), enabling optogenetic stimulation of single GABAergic neurons and recordings of unitary synaptic events in pyramidal neurons. Quantal analysis revealed that learning‐induced enhanced inhibition is mediated by increased quantal size of the evoked inhibitory events. Next, we examined the plasticity of synaptic inhibition induced by long‐lasting, intrinsically evoked spike firing in post‐synaptic neurons. Repetitive depolarizing current pulses from depolarized (−70 mV) or hyperpolarized (−90 mV) membrane potentials induced long‐term depression (LTD) and long‐term potentiation (LTP) of synaptic inhibition, respectively. We found a profound bidirectional increase in the ability to induce both LTD, mediated by L‐type calcium channels, and LTP, mediated by R‐type calcium channels after rule learning. Blocking the GABAB receptor reversed the effect of intrinsic stimulation at −90 mV from LTP to LTD. We suggest that learning greatly enhances the ability to modify the strength of synaptic inhibition of principal neurons in both directions. Such plasticity of synaptic plasticity allows fine‐tuning of inhibition on each particular neuron, thereby stabilizing the network while maintaining the memory of the rule. imageKey points Olfactory discrimination rule learning results in long‐lasting enhancement of synaptic inhibition on piriform cortex pyramidal neurons. Quantal analysis of unitary inhibitory synaptic events, evoked by optogenetic minimal stimulation, revealed that enhanced synaptic inhibition is mediated by increased quantal size. Surprisingly, metaplasticity of synaptic inhibition, induced by intrinsically evoked repetitive spike firing, is increased bidirectionally. The susceptibility to both long‐term depression (LTD) and long‐term potentiation (LTP) of inhibition is enhanced after learning. LTD of synaptic inhibition is mediated by L‐type calcium channels and LTP by R‐type calcium channels. LTP is also dependent on activation of GABAB receptors. We suggest that learning‐induced changes in the metaplasticity of synaptic inhibition enable the fine‐tuning of inhibition on each particular neuron, thereby stabilizing the network while maintaining the memory of the rule.

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Reversing Aging: Decline in Complex Olfactory Learning Can be Rectified by Restoring Intrinsic Plasticity of Hippocampal CA1 Pyramidal Neurons

Cited by 2 publications

References 40 publications

Two Signaling Modes Are Better than One: Flux-Independent Signaling by Ionotropic Glutamate Receptors Is Coming of Age

Two Signaling Modes Are Better than One: Flux-Independent Signaling by Ionotropic Glutamate Receptors Is Coming of Age

Learning‐induced bidirectional enhancement of inhibitory synaptic metaplasticity

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