scholarly journals LRRK2 at the presynaptic site: a 16‐years perspective

2020 ◽  
Author(s):  
Francesca Pischedda ◽  
Giovanni Piccoli
Keyword(s):  
Presynaptic Site

scholarly journals Cholinergic Regulation of the Posterior Medial Thalamic Nucleus

2006 ◽  
Vol 96 (5) ◽  
pp. 2265-2273 ◽  
Author(s):  
Radi Masri ◽  
Jason C. Trageser ◽  
Tatiana Bezdudnaya ◽  
Ying Li ◽  
Asaf Keller
Keyword(s):  
Brain Stem ◽  
Cholinergic System ◽  
Somatosensory System ◽  
Zona Incerta ◽  
State Dependent ◽  
Presynaptic Site ◽  
Behavioral States ◽  
Flow Of Information ◽  
The Brain

We previously showed that the GABAergic nucleus zona incerta (ZI) suppresses vibrissae-evoked responses in the posterior medial (POm) thalamus of the rodent somatosensory system. We proposed that this inhibitory incertothalamic pathway regulates POm responses during different behavioral states. Here we tested the hypothesis that this pathway is modulated by the ascending brain stem cholinergic system, which regulates sleep–wake cycles and states of vigilance. We demonstrate that cholinergic inputs facilitate POm responses to vibrissae stimulation. Activation of the cholinergic system by stimulation of brain stem cholinergic nuclei (laterodorsal tegmental and the pedunculopontine tegmental) or by tail pinch significantly increased the magnitude of POm responses to vibrissae stimulation. Microiontophoresis of the muscarinic receptor agonist carbachol enhanced POm responses to vibrissae stimulation. Application of carbachol to an in vitro slice preparation reduced the frequency but not the amplitude of miniature inhibitory postsynaptic currents, indicating a presynaptic site of action for carbachol. We conclude that the cholinergic system facilitates POm responses by suppressing GABAergic inputs from ZI. We propose the state-dependent gating hypothesis, which asserts that differing behavioral states, regulated by the brain stem cholinergic system, modulate the flow of information through POm.

scholarly journals Presynaptic serotonin 2A receptors modulate thalamocortical plasticity and associative learning

2016 ◽  
Vol 113 (10) ◽  
pp. E1382-E1391 ◽  
Author(s):  
Alexander Barre ◽  
Coralie Berthoux ◽  
Dimitri De Bundel ◽  
Emmanuel Valjent ◽  
Joël Bockaert ◽  
...  
Keyword(s):  
Receptor Activation ◽  
Network Activity ◽  
Viral Gene ◽  
Mediodorsal Thalamus ◽  
Presynaptic Site ◽  
Postsynaptic Site ◽  
Viral Gene Delivery ◽  
Serotonin 2A ◽  
Delivery Approach

Higher-level cognitive processes strongly depend on a complex interplay between mediodorsal thalamus nuclei and the prefrontal cortex (PFC). Alteration of thalamofrontal connectivity has been involved in cognitive deficits of schizophrenia. Prefrontal serotonin (5-HT)2A receptors play an essential role in cortical network activity, but the mechanism underlying their modulation of glutamatergic transmission and plasticity at thalamocortical synapses remains largely unexplored. Here, we show that 5-HT2A receptor activation enhances NMDA transmission and gates the induction of temporal-dependent plasticity mediated by NMDA receptors at thalamocortical synapses in acute PFC slices. Expressing 5-HT2A receptors in the mediodorsal thalamus (presynaptic site) of 5-HT2A receptor-deficient mice, but not in the PFC (postsynaptic site), using a viral gene-delivery approach, rescued the otherwise absent potentiation of NMDA transmission, induction of temporal plasticity, and deficit in associative memory. These results provide, to our knowledge, the first physiological evidence of a role of presynaptic 5-HT2A receptors located at thalamocortical synapses in the control of thalamofrontal connectivity and the associated cognitive functions.

Presynaptic dysfunction in Parkinson's disease: a focus on LRRK2

2012 ◽  
Vol 40 (5) ◽  
pp. 1111-1116 ◽  
Author(s):  
Elisa Belluzzi ◽  
Elisa Greggio ◽  
Giovanni Piccoli
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Models ◽  
Critical Role ◽  
Dopamine Turnover ◽  
Presynaptic Neuron ◽  
Presynaptic Site ◽  
Promising Target ◽  
Key Factor ◽  
Trafficking Defects

PD (Parkinson's disease) is a common neurodegenerative disease clinically characterized by bradykinesia, rigidity and resting tremor. Recent studies have proposed that synaptic dysfunction, implicated in numerous studies of animal models of PD, might be a key factor in PD. The molecular defects that lead to PD progression might be hidden at the presynaptic neuron: in fact accumulating evidence has shown that the majority of the genes linked to PD play a critical role at the presynaptic site. In the present paper, we focus on the presynaptic function of LRRK2 (leucine-rich repeat kinase 2), a protein that mutated represents the main genetic cause of familial PD described to date. Neurotransmission relies on proper presynaptic vesicle trafficking; defects in this process, variation in dopamine flow and alteration of presynaptic plasticity have been reported in several animal models of LRRK2 mutations. Furthermore, impaired dopamine turnover has been described in presymptomatic LRRK2 PD patients. Thus, given the pathological events occurring at the synapses of PD patients, the presynaptic site may represent a promising target for early diagnostic therapeutic intervention.

Learning Rule of Homeostatic Synaptic Scaling: Presynaptic Dependent or Not

2011 ◽  
Vol 23 (12) ◽  
pp. 3145-3161 ◽  
Author(s):  
Jian K. Liu
Keyword(s):  
Recurrent Neural Networks ◽  
Learning Rule ◽  
Network Activity ◽  
Matrix Analysis ◽  
Transition Matrices ◽  
Synaptic Scaling ◽  
Stable Regime ◽  
Learning Rules ◽  
Presynaptic Site ◽  
The Stability

It has been established that homeostatic synaptic scaling plasticity can maintain neural network activity in a stable regime. However, the underlying learning rule for this mechanism is still unclear. Whether it is dependent on the presynaptic site remains a topic of debate. Here we focus on two forms of learning rules: traditional synaptic scaling (SS) without presynaptic effect and presynaptic-dependent synaptic scaling (PSD). Analysis of the synaptic matrices reveals that transition matrices between consecutive synaptic matrices are distinct: they are diagonal and linear to neural activity under SS, but become nondiagonal and nonlinear under PSD. These differences produce different dynamics in recurrent neural networks. Numerical simulations show that network dynamics are stable under PSD but not SS, which suggests that PSD is a better form to describe homeostatic synaptic scaling plasticity. Matrix analysis used in the study may provide a novel way to examine the stability of learning dynamics.

scholarly journals Catecholamine-stimulated cyclic GMP accumulation in the rat pineal: apparent presynaptic site of action.

1976 ◽  
Vol 73 (10) ◽  
pp. 3398-3402 ◽  
Author(s):  
R. F. O'Dea ◽  
M. Zatz
Keyword(s):  
Cyclic Gmp ◽  
Presynaptic Site ◽  
Site Of Action

scholarly journals Imidazoleacetic acid-ribotide induces depression of synaptic responses in hippocampus through activation of imidazoline receptors

2011 ◽  
Vol 105 (3) ◽  
pp. 1266-1275 ◽  
Author(s):  
O. Bozdagi ◽  
X. B. Wang ◽  
G. P. Martinelli ◽  
G. Prell ◽  
V. L. Friedrich ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Synaptic Transmission ◽  
Hippocampal Slices ◽  
Synaptic Depression ◽  
Mammalian Brain ◽  
Imidazoline Receptors ◽  
Excitatory Transmission ◽  
Presynaptic Site ◽  
Whole Cell Recordings ◽  
Synaptic Responses

Imidazole-4-acetic acid-ribotide (IAA-RP), an endogenous agonist at imidazoline receptors (I-Rs), is a putative neurotransmitter/regulator in mammalian brain. We studied the effects of IAA-RP on excitatory transmission by performing extracellular and whole cell recordings at Schaffer collateral-CA1 synapses in rat hippocampal slices. Bath-applied IAA-RP induced a concentration-dependent depression of synaptic transmission that, after washout, returned to baseline within 20 min. Maximal decrease occurred with 10 μM IAA-RP, which reduced the slope of field extracellular postsynaptic potentials (fEPSPs) to 51.2 ± 5.7% of baseline at 20 min of exposure. Imidazole-4-acetic acid-riboside (IAA-R; 10 μM), the endogenous dephosphorylated metabolite of IAA-RP, also produced inhibition of fEPSPs. This effect was smaller than that produced by IAA-RP (to 65.9 ± 3.8% of baseline) and occurred after a further 5- to 8-min delay. The frequency, but not the amplitude, of miniature excitatory postsynaptic currents was decreased, and paired-pulse facilitation (PPF) was increased after application of IAA-RP, suggesting a principally presynaptic site of action. Since IAA-RP also has low affinity for α2-adrenergic receptors (α2-ARs), we tested synaptic depression induced by IAA-RP in the presence of α2-ARs, I1-R, or I3-R antagonists. The α2-AR antagonist rauwolscine (100 nM), which blocked the actions of the α2-AR agonist clonidine, did not affect either the IAA-RP-induced synaptic depression or the increase in PPF. In contrast, efaroxan (50 μM), a mixed I1-R and α2-AR antagonist, abolished the synaptic depression induced by IAA-RP and abolished the related increase in PPF. KU-14R, an I3-R antagonist, partially attenuated responses to IAA-RP. Taken together, these data support a role for IAA-RP in modulating synaptic transmission in the hippocampus through activation of I-Rs.

Isoflurane Reduces Glutamatergic Transmission in Neurons in the Spinal Cord Superficial Dorsal Horn: Evidence for a Presynaptic Site of an Analgesic Action

2004 ◽  
pp. 1718-1723 ◽  
Author(s):  
Rainer Haseneder ◽  
J??rge Kurz ◽  
Hans-Ulrich U. Dodt ◽  
Eberhard Kochs ◽  
Walter Zieglg??nsberger ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Superficial Dorsal Horn ◽  
Analgesic Action ◽  
Glutamatergic Transmission ◽  
Presynaptic Site

A presynaptic site of action of substance P and vasoactive intestinal polypeptide on myenteric neurons

1985 ◽  
Vol 330 (2) ◽  
pp. 382-385 ◽  
Author(s):  
W.M. Yau ◽  
M.L. Youther ◽  
P.R. Verdun
Keyword(s):  
Substance P ◽  
Vasoactive Intestinal Polypeptide ◽  
Myenteric Neurons ◽  
Presynaptic Site ◽  
Site Of Action ◽  
Intestinal Polypeptide

scholarly journals Concentration-Invariant Odor Representation in the Olfactory System by Presynaptic Inhibition

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Danke Zhang ◽  
Yuanqing Li ◽  
Si Wu
Keyword(s):  
Olfactory Receptor ◽  
Olfactory System ◽  
Olfactory Receptor Neurons ◽  
Projection Neurons ◽  
Invariant Representation ◽  
Odor Concentration ◽  
Presynaptic Site ◽  
Divisive Normalization ◽  
Receptor Neurons ◽  
Parameter Condition

The present study investigates a network model for implementing concentration-invariant representation for odors in the olfactory system. The network consists of olfactory receptor neurons, projection neurons, and inhibitory local neurons. Receptor neurons send excitatory inputs to projection neurons, which are modulated by the inhibitory inputs from local neurons. The modulation occurs at the presynaptic site from a receptor neuron to a projection one, leading to the operation of divisive normalization. The responses of local interneurons are determined by the total activities of olfactory receptor neurons. We find that with a proper parameter condition, the responses of projection neurons become effectively independent of the odor concentration. Simulation results confirm our theoretical analysis.

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