Long term potentiation of mossy fiber feedforward inhibition of CA3 pyramidal cells maintains E/I balance in epilepsy model

The application of tetraethylammonium (TEA), a blocker of voltage-dependent potassium channels, can induce long-term potentiation (LTP) in the synaptic systems CA3–CA1 and mossy fiber-CA3 pyramidal cells of the hippocampus. In the mossy fibers, the depolarization evoked by extracellular TEA induces a large amount of glutamate and also of zinc release. It is considered that zinc has a neuromodulatory role at the mossy fiber synapses, which can, at least in part, be due to the activation of presynaptic ATP-dependent potassium (KATP) channels. The aim of this work was to study properties of TEA-induced zinc signals, detected at the mossy fiber region, using the permeant form of the zinc indicator Newport Green. The application of TEA caused a depression of those signals that was partially blocked by the KATP channel inhibitor tolbutamide. After the removal of TEA, the signals usually increased to a level above baseline. These results are in agreement with the idea that intense zinc release during strong synaptic events triggers a negative feedback action. The zinc depression, caused by the LTP-evoking chemical stimulation, turns into potentiation after TEA washout, suggesting the existence of a correspondence between the observed zinc potentiation and TEA-evoked mossy fiber LTP.

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Kv1.2 contributes to pattern separation by regulating the hippocampal CA3 neuronal ensemble size

10.1101/2020.07.21.213538 ◽

2020 ◽

Author(s):

Kisang Eom ◽

Hyoung Ro Lee ◽

Jung Ho Hyun ◽

Hyun-Hee Ryu ◽

Yong-Seok Lee ◽

...

Keyword(s):

Pyramidal Cells ◽

Long Term Potentiation ◽

Pattern Separation ◽

Ensemble Size ◽

Contextual Fear ◽

Term Potentiation ◽

Hippocampal Ca3 ◽

Plastic Changes ◽

Ca3 Pyramidal Cells

AbstractKv1.2 expression in rodent CA3 pyramidal cells (CA3-PC) is polarized to distal apical dendrites, and regulate the synaptic responses to perforant pathway (PP) inputs. Accordingly, Kv1.2 haploinsufficiency (Kcna2+/−) in CA3-PCs, but not Kv1.1 (Kcna1+/−), lowered the threshold for long-term potentiation at PP-CA3 synapses. The Kcna2+/− mice, but not Kcna1+/−, displayed impairments in contextual fear discrimination task. The size and overlap of CA3 ensembles activated by the first visits to slightly different contexts were not different between wildtype and Kcna2+/− mice, but these ensemble parameters diverged over training days between genotypes, suggesting abnormal plastic changes in the CA3 network of Kcna2+/− mice. Eventually, the Kcna2+/− mice exhibited larger ensemble size and overlap upon retrieval of two contexts, compared to wildtype or Kcna1+/− mice. These results suggest that Kv1.2 subunits prevent promiscuous plastic changes at PP-CA3 synapses, and contribute to sparse representation of memories and pattern separation in the CA3 network.

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M2 muscarinic acetylcholine receptors regulate long-term potentiation at hippocampal CA3 pyramidal cell synapses in an input-specific fashion

Journal of Neurophysiology ◽

10.1152/jn.00740.2011 ◽

2012 ◽

Vol 108 (1) ◽

pp. 91-100 ◽

Cited By ~ 16

Author(s):

Fang Zheng ◽

Jürgen Wess ◽

Christian Alzheimer

Keyword(s):

Muscarinic Receptor ◽

Pyramidal Cells ◽

Long Term Potentiation ◽

Receptor Subtypes ◽

Muscarinic Receptor Subtypes ◽

Short Term ◽

Term Potentiation ◽

Hippocampal Ca3 ◽

Ca3 Pyramidal Cells

Muscarinic receptors have long been known as crucial players in hippocampus-dependent learning and memory, but our understanding of the cellular underpinnings and the receptor subtypes involved lags well behind. This holds in particular for the hippocampal CA3 region, where the mechanisms of synaptic plasticity depend on the type of afferent input. Williams and Johnston (Williams S, Johnston D. Science 242: 84–87, 1988; Williams S, Johnston D. J Neurophysiol 64: 1089–1097, 1990) demonstrated muscarinic depression of mossy fiber (MF) long-term potentiation (LTP) through a presynaptic site of action and Maeda et al. (Maeda T, Kaneko S, Satoh M. Brain Res 619: 324–330, 1993) proposed a bidirectional modulation of MF LTP by muscarinic receptor subtypes. Since then, this issue, as well as muscarinic regulation of plasticity at associational/commissural (A/C) fiber-CA3 synapses has remained largely neglected, not least because of the lack of highly selective ligands for the different muscarinic receptor subtypes. In the present study, we performed field potential and whole cell recordings from the hippocampal CA3 region of M2 receptor knockout mice to determine the role of M2 receptors in short-term and long-term plasticity at A/C and MF inputs to CA3 pyramidal cells. At the A/C synapse, M2 receptors promoted short-term facilitation and LTP. Unexpectedly, M2 receptors mediated the opposite effect on LTP at the MF synapse, which was significantly reduced, most likely involving a depressant effect of M2 receptors on adenylyl cyclase activity in MF terminals. Our data demonstrate that cholinergic projections recruit M2 receptors to redistribute the gain of LTP in CA3 pyramidal cells in an input-specific manner.

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Protein kinase C injection into hippocampal pyramidal cells elicits features of long term potentiation

Nature ◽

10.1038/328426a0 ◽

1987 ◽

Vol 328 (6129) ◽

pp. 426-429 ◽

Cited By ~ 251

Author(s):

G.-Y. Hu ◽

Ø. Hvalby ◽

S. I. Walaas ◽

K. A. Albert ◽

P. Skjeflo ◽

...

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Pyramidal Cells ◽

Long Term Potentiation ◽

Kinase C ◽

Term Potentiation ◽

Hippocampal Pyramidal Cells

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Selective Induction of LTP and LTD by Postsynaptic [Ca2+]i Elevation

Journal of Neurophysiology ◽

10.1152/jn.1999.81.2.781 ◽

1999 ◽

Vol 81 (2) ◽

pp. 781-787 ◽

Cited By ~ 311

Author(s):

Shao-Nian Yang ◽

Yun-Gui Tang ◽

Robert S. Zucker

Keyword(s):

Calcium Concentration ◽

Pyramidal Cells ◽

Long Term Potentiation ◽

Biological Information ◽

Synaptic Modulation ◽

Ca1 Pyramidal Cells ◽

Caged Calcium ◽

Term Potentiation ◽

Calcium Compound

Selective Induction of LTP and LTD by Postsynaptic [Ca2+]i Elevation. Long-term potentiation (LTP) and long-term depression (LTD), two prominent forms of synaptic plasticity at glutamatergic afferents to CA1 hippocampal pyramidal cells, are both triggered by the elevation of postsynaptic intracellular calcium concentration ([Ca2+]i). To understand how one signaling molecule can be responsible for triggering two opposing forms of synaptic modulation, different postsynaptic [Ca2+]i elevation patterns were generated by a new caged calcium compound nitrophenyl-ethylene glycol-bis(β-aminoethyl ether)- N, N, N′, N′-tetraacetic acid in CA1 pyramidal cells. We found that specific patterns of [Ca2+]i elevation selectively activate LTP or LTD. In particular, only LTP was triggered by a brief increase of [Ca2+]i with relatively high magnitude, which mimics the [Ca2+]i rise during electrical stimulation typically used to induce LTP. In contrast, a prolonged modest rise of [Ca2+]i reliably induced LTD. An important implication of the results is that both the amplitude and the duration of an intracellular chemical signal can carry significant biological information.

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