Recruitment of N-Type Ca2+ Channels during LTP Enhances Low Release Efficacy of Hippocampal CA1 Perforant Path Synapses

Ahmed, Mohsin; Siegelbaum, Steven A.

doi:10.1016/j.neuron.2009.07.013

Cited by 68 publications

(75 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We now show that the recruitment of a presynaptic expression mechanism further distinguishes LTP2 and LTP3 from LTP1. Using a more precise categorization of LTP with well-characterized and discrete mechanisms, our results elaborate on previous studies that showed persistent forms of LTP are associated with presynaptic functional changes (Huang and Kandel 1994;Zakharenko et al 2001Zakharenko et al , 2003Huang et al 2005;Stanton et al 2005;Ahmed and Siegelbaum 2009). …”

Section: Discussionsupporting

confidence: 78%

A protein synthesis and nitric oxide-dependent presynaptic enhancement in persistent forms of long-term potentiation

Johnstone¹,

Raymond²

2011

Learn. Mem.

View full text Add to dashboard Cite

Long-term potentiation (LTP) is an important process underlying learning and memory in the brain. At CA3-CA1 synapses in the hippocampus, three discrete forms of LTP (LTP1, 2, and 3) can be differentiated on the basis of maintenance and induction mechanisms. However, the relative roles of pre-and post-synaptic expression mechanisms in LTP1, 2, and 3 are unknown. Neurotransmitter release in the expression of LTP1, 2, and 3 was measured via FM 1 -43 destaining from CA3 terminals in hippocampal slices from male Wistar rats (7 -8 wk). No difference in vesicle turnover rate was observed for LTP1 up to 160 min following induction by one train of theta-burst stimulation (1TBS). A presynaptic enhancement was found for LTP2 at 160 min after induction by 4TBS, and for LTP3 at both 80 and 160 min after induction by 8TBS. Inhibition of nitric oxide (NO) signaling blocked both LTP2 and LTP3 maintenance and the associated enhanced release. LTP2 maintenance and its presynaptic expression were dependent on protein synthesis, but not gene transcription. LTP3 maintenance was dependent on both translation and transcription, but like LTP2, the enhanced release only required translation. These data considerably strengthen the mechanistic separation of LTP1, 2, and 3, supporting a model of multiple, discrete forms of LTP at CA3-CA1 synapses rather than different temporal phases.

show abstract

Section: Discussionsupporting

confidence: 78%

A protein synthesis and nitric oxide-dependent presynaptic enhancement in persistent forms of long-term potentiation

Johnstone¹,

Raymond²

2011

Learn. Mem.

View full text Add to dashboard Cite

show abstract

“…LTP was first described in the hippocampus by Bliss and Lømo in 1973 [63] and has been extensively studied at the CA3-CA1 Schaeffer collateral synapse. More recently, LTP has been characterized at synapses between CA3 and CA2 [9,58] at proximal dendrites in the SR, at synapses between cortical inputs and the distal CA1 dendrite in the SLM [64][65][66] and between cortical inputs and the distal CA2 dendrites in the SLM [9]. As already described for other inputs, these results confirm the general idea that synaptic plasticity is different not only between different inputs, but also between different targets contacted by the same input.…”

Section: Synaptic Plasticitysupporting

confidence: 82%

Synaptic integration by different dendritic compartments of hippocampal CA1 and CA2 pyramidal neurons

Piskorowski

Chevaleyre

2011

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

Pyramidal neurons have a complex dendritic arbor containing tens of thousands of synapses. In order for the somatic/axonal membrane potential to reach action potential threshold, concurrent activation of multiple excitatory synapses is required. Frequently, instead of a simple algebraic summation of synaptic potentials in the soma, different dendritic compartments contribute to the integration of multiple inputs, thus endowing the neuron with a powerful computational ability. Most pyramidal neurons share common functional properties. However, different and sometimes contrasting dendritic integration rules are also observed. In this review, we focus on the dendritic integration of two neighboring pyramidal neurons in the hippocampus: the well-characterized CA1 and the much less understood CA2. The available data reveal that the dendritic integration of these neurons is markedly different even though they are targeted by common inputs at similar locations along their dendrites. This contrasting dendritic integration results in different routing of information flow and generates different corticohippocampal loops.

show abstract

“…The Rho-GTPase Cdc42 has been identified as a crucial component of the signalling machinery underlying long-term homeostatic scaling of presynaptic release probability at the Drosophila neuromuscular junction [57]. Interestingly, both Cdc42-dependent homeostatic scaling and different forms of presynaptic LTP converge upon regulation of presynaptic voltage-dependent calcium channels [35,57,58]. This may suggest that lack of OPHN1 might result in a profound dysfunction of presynaptic regulatory signalling systems contributing to both long-term homeostatic and Hebbian forms of plasticity.…”

Section: Discussionmentioning

confidence: 99%

Lack of the presynaptic RhoGAP protein oligophrenin1 leads to cognitive disabilities through dysregulation of the cAMP/PKA signalling pathway

Khelfaoui

Gambino

Houbaert

et al. 2014

Phil. Trans. R. Soc. B

View full text Add to dashboard Cite

Loss-of-function mutations in the gene encoding for the RhoGAP protein of oligophrenin-1 (OPHN1) lead to cognitive disabilities (CDs) in humans, yet the underlying mechanisms are not known. Here, we show that in mice constitutive lack of Ophn1 is associated with dysregulation of the cyclic adenosine monophosphate/phosphate kinase A (cAMP/PKA) signalling pathway in a brain-area-specific manner. Consistent with a key role of cAMP/PKA signalling in regulating presynaptic function and plasticity, we found that PKA-dependent presynaptic plasticity was completely abolished in affected brain regions, including hippocampus and amygdala. At the behavioural level, lack of OPHN1 resulted in hippocampus- and amygdala-related learning disabilities which could be fully rescued by the ROCK/PKA kinase inhibitor fasudil. Together, our data identify OPHN1 as a key regulator of presynaptic function and suggest that, in addition to reported postsynaptic deficits, loss of presynaptic plasticity contributes to the pathophysiology of CDs.

show abstract

Recruitment of N-Type Ca2+ Channels during LTP Enhances Low Release Efficacy of Hippocampal CA1 Perforant Path Synapses

Cited by 68 publications

References 70 publications

A protein synthesis and nitric oxide-dependent presynaptic enhancement in persistent forms of long-term potentiation

A protein synthesis and nitric oxide-dependent presynaptic enhancement in persistent forms of long-term potentiation

Synaptic integration by different dendritic compartments of hippocampal CA1 and CA2 pyramidal neurons

Lack of the presynaptic RhoGAP protein oligophrenin1 leads to cognitive disabilities through dysregulation of the cAMP/PKA signalling pathway

Contact Info

Product

Resources

About