scholarly journals A combined computational and intracellular study of correlated synaptic bombardment in neocortical pyramidal neurons in vivo

2000 ◽  
Vol 32-33 ◽  
pp. 113-119 ◽  
Author(s):  
Alain Destexhe ◽  
Denis Paré
Keyword(s):  
Pyramidal Neurons ◽  
Intracellular Study ◽  
Neocortical Pyramidal Neurons

scholarly journals Ciliary neuropeptidergic signaling dynamically regulates excitatory synapses in postnatal neocortical pyramidal neurons

2020 ◽  
Author(s):  
Lauren Tereshko ◽  
Ya Gao ◽  
Brian A. Cary ◽  
Gina G. Turrigiano ◽  
Piali Sengupta
Keyword(s):  
Primary Cilia ◽  
Neuronal Development ◽  
Pyramidal Neurons ◽  
Somatostatin Receptor ◽  
Cognitive Disorders ◽  
Mammalian Brain ◽  
Excitatory Synapses ◽  
Ciliary Signaling ◽  
Neocortical Pyramidal Neurons

ABSTRACTPrimary cilia are compartmentalized sensory organelles present on the majority of neurons in the mammalian brain throughout adulthood. Recent evidence suggests that cilia regulate multiple aspects of neuronal development, including the maintenance of neuronal connectivity. However, whether ciliary signals can dynamically modulate postnatal circuit excitability is unknown. Here we show that acute cell-autonomous knockdown of ciliary signaling rapidly strengthens glutamatergic inputs onto cultured neocortical pyramidal neurons, and increases spontaneous firing. This increased excitability occurs without changes to passive neuronal properties or intrinsic excitability. Further, the neuropeptide receptor somatostatin receptor 3 (SSTR3) is localized nearly exclusively to pyramidal neuron cilia both in vivo and in culture, and pharmacological manipulation of SSTR3 signaling bidirectionally modulates excitatory synaptic inputs onto these neurons. Our results indicate that ciliary neuropeptidergic signaling dynamically modulates excitatory synapses, and suggest that defects in this regulation may underlie a subset of behavioral and cognitive disorders associated with ciliopathies.

In vivo dendritic calcium dynamics in neocortical pyramidal neurons

Nature ◽  
1997 ◽  
Vol 385 (6612) ◽  
pp. 161-165 ◽  
Author(s):  
Karel Svoboda ◽  
Winfried Denk ◽  
David Kleinfeld ◽  
David W. Tank
Keyword(s):  
Pyramidal Neurons ◽  
Calcium Dynamics ◽  
Neocortical Pyramidal Neurons

scholarly journals Synaptic Background Activity Enhances the Responsiveness of Neocortical Pyramidal Neurons

2000 ◽  
Vol 84 (3) ◽  
pp. 1488-1496 ◽  
Author(s):  
Nicolas Hô ◽  
Alain Destexhe
Keyword(s):  
Pyramidal Neurons ◽  
Background Activity ◽  
Detection Threshold ◽  
Population Level ◽  
Dendritic Morphology ◽  
Voltage Fluctuations ◽  
Active Conductance ◽  
Cellular Responsiveness ◽  
Neocortical Pyramidal Neurons

Neocortical pyramidal neurons in vivo are subject to an intense synaptic background activity but little is known of how this activity affects cellular responsiveness and what function it may serve. These issues were examined in morphologically reconstructed neocortical pyramidal neurons in which synaptic background activity was simulated based on recent measurements in cat parietal cortex. We show that background activity can be decomposed into two components: a tonically active conductance and voltage fluctuations. Previous studies have mostly focused on the conductance effect, revealing that background activity is responsible for a decrease in responsiveness, which imposes severe conditions of coincidence of inputs necessary to discharge the cell. It is shown here, in contrast, that responsiveness is enhanced if voltage fluctuations are taken into account; in this case the model can produce responses to inputs that would normally be subthreshold. This effect is analyzed by dissecting and comparing the different components of background activity, as well as by evaluating the contribution of parameters such as the dendritic morphology, the distribution of leak currents, the value of axial resistivity, the densities of voltage-dependent currents, and the release parameters underlying background activity. Interestingly, the model's optimal responsiveness was obtained when voltage fluctuations were of the same order as those measured intracellularly in vivo. Possible consequences were also investigated at the population level, where the presence of background activity allowed networks of pyramidal neurons to instantaneously detect inputs that are small compared with the classical detection threshold. These results suggest, at the single-cell level, that the presence of voltage fluctuations has a determining influence on cellular responsiveness and that these should be taken into account in models of background activity. At the network level, we predict that background activity provides the necessary drive for detecting events that would normally be undetectable. Experiments are suggested to explore this possible functional role for background activity.

In vivo function of Rnd2 in the development of neocortical pyramidal neurons

2006 ◽  
Vol 54 (2) ◽  
pp. 149-153 ◽  
Author(s):  
Kazuhiro Nakamura ◽  
Yoko Yamashita ◽  
Nobuaki Tamamaki ◽  
Hironori Katoh ◽  
Takeshi Kaneko ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Neocortical Pyramidal Neurons

scholarly journals Ciliary neuropeptidergic signaling dynamically regulates excitatory synapses in postnatal neocortical pyramidal neurons

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Lauren Tereshko ◽  
Ya Gao ◽  
Brian A Cary ◽  
Gina G Turrigiano ◽  
Piali Sengupta
Keyword(s):  
Primary Cilia ◽  
Neuronal Development ◽  
Pyramidal Neurons ◽  
Somatostatin Receptor ◽  
Cognitive Disorders ◽  
Mammalian Brain ◽  
Excitatory Synapses ◽  
Ciliary Signaling ◽  
Neocortical Pyramidal Neurons

Primary cilia are compartmentalized sensory organelles present on the majority of neurons in the mammalian brain throughout adulthood. Recent evidence suggests that cilia regulate multiple aspects of neuronal development, including the maintenance of neuronal connectivity. However, whether ciliary signals can dynamically modulate postnatal circuit excitability is unknown. Here we show that acute cell-autonomous knockdown of ciliary signaling rapidly strengthens glutamatergic inputs onto cultured rat neocortical pyramidal neurons and increases spontaneous firing. This increased excitability occurs without changes to passive neuronal properties or intrinsic excitability. Further, the neuropeptide receptor somatostatin receptor 3 (SSTR3) is localized nearly exclusively to excitatory neuron cilia both in vivo and in culture, and pharmacological manipulation of SSTR3 signaling bidirectionally modulates excitatory synaptic inputs onto these neurons. Our results indicate that ciliary neuropeptidergic signaling dynamically modulates excitatory synapses and suggest that defects in this regulation may underlie a subset of behavioral and cognitive disorders associated with ciliopathies.

Impact of Spontaneous Synaptic Activity on the Resting Properties of Cat Neocortical Pyramidal Neurons In Vivo

1998 ◽  
Vol 79 (3) ◽  
pp. 1450-1460 ◽  
Author(s):  
Denis Paré ◽  
Eric Shink ◽  
Hélène Gaudreau ◽  
Alain Destexhe ◽  
Eric J. Lang
Keyword(s):  
Cortical Neurons ◽  
Pyramidal Neurons ◽  
Brain Slices ◽  
Synaptic Activity ◽  
Intact Brain ◽  
Lower Temperature ◽  
The Impact ◽  
Neocortical Pyramidal Neurons

Paré, Denis, Eric Shink, Hélène Gaudreau, Alain Destexhe, and Eric J. Lang. Impact of spontaneous synaptic activity on the resting properties of cat neocortical pyramidal neurons in vivo. J. Neurophysiol. 79: 1450–1460, 1998. The frequency of spontaneous synaptic events in vitro is probably lower than in vivo because of the reduced synaptic connectivity present in cortical slices and the lower temperature used during in vitro experiments. Because this reduction in background synaptic activity could modify the integrative properties of cortical neurons, we compared the impact of spontaneous synaptic events on the resting properties of intracellularly recorded pyramidal neurons in vivo and in vitro by blocking synaptic transmission with tetrodotoxin (TTX). The amount of synaptic activity was much lower in brain slices (at 34°C), as the standard deviation of the intracellular signal was 10–17 times lower in vitro than in vivo. Input resistances ( R ins) measured in vivo during relatively quiescent epochs (“control R ins”) could be reduced by up to 70% during periods of intense spontaneous activity. Further, the control R ins were increased by ∼30–70% after TTX application in vivo, approaching in vitro values. In contrast, TTX produced negligible R in changes in vitro (∼4%). These results indicate that, compared with the in vitro situation, the background synaptic activity present in intact networks dramatically reduces the electrical compactness of cortical neurons and modifies their integrative properties. The impact of the spontaneous synaptic bombardment should be taken into account when extrapolating in vitro findings to the intact brain.

scholarly journals Impact of Network Activity on the Integrative Properties of Neocortical Pyramidal Neurons In Vivo

1999 ◽  
Vol 81 (4) ◽  
pp. 1531-1547 ◽  
Author(s):  
Alain Destexhe ◽  
Denis Paré
Keyword(s):  
High Frequency ◽  
Pyramidal Neurons ◽  
Synaptic Activity ◽  
Network Activity ◽  
Synaptic Inputs ◽  
Neocortical Neurons ◽  
Voltage Dependent ◽  
The Impact ◽  
Neocortical Pyramidal Neurons

Impact of network activity on the integrative properties of neocortical pyramidal neurons in vivo. During wakefulness, neocortical neurons are subjected to an intense synaptic bombardment. To assess the consequences of this background activity for the integrative properties of pyramidal neurons, we constrained biophysical models with in vivo intracellular data obtained in anesthetized cats during periods of intense network activity similar to that observed in the waking state. In pyramidal cells of the parietal cortex (area 5–7), synaptic activity was responsible for an approximately fivefold decrease in input resistance ( R in), a more depolarized membrane potential ( V m), and a marked increase in the amplitude of V m fluctuations, as determined by comparing the same cells before and after microperfusion of tetrodotoxin (TTX). The model was constrained by measurements of R in, by the average value and standard deviation of the V m measured from epochs of intense synaptic activity recorded with KAc or KCl-filled pipettes as well as the values measured in the same cells after TTX. To reproduce all experimental results, the simulated synaptic activity had to be of relatively high frequency (1–5 Hz) at excitatory and inhibitory synapses. In addition, synaptic inputs had to be significantly correlated (correlation coefficient ∼0.1) to reproduce the amplitude of V m fluctuations recorded experimentally. The presence of voltage-dependent K+ currents, estimated from current-voltage relations after TTX, affected these parameters by <10%. The model predicts that the conductance due to synaptic activity is 7–30 times larger than the somatic leak conductance to be consistent with the approximately fivefold change in R in. The impact of this massive increase in conductance on dendritic attenuation was investigated for passive neurons and neurons with voltage-dependent Na+/K+ currents in soma and dendrites. In passive neurons, correlated synaptic bombardment had a major influence on dendritic attenuation. The electrotonic attenuation of simulated synaptic inputs was enhanced greatly in the presence of synaptic bombardment, with distal synapses having minimal effects at the soma. Similarly, in the presence of dendritic voltage-dependent currents, the convergence of hundreds of synaptic inputs was required to evoke action potentials reliably. In this case, however, dendritic voltage-dependent currents minimized the variability due to input location, with distal apical synapses being as effective as synapses on basal dendrites. In conclusion, this combination of intracellular and computational data suggests that, during low-amplitude fast electroencephalographic activity, neocortical neurons are bombarded continuously by correlated synaptic inputs at high frequency, which significantly affect their integrative properties. A series of predictions are suggested to test this model.

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