Estimation of synaptic conductances and their variances from intracellular recordings of neocortical neurons in vivo

2004 ◽  
Vol 58-60 ◽  
pp. 387-392 ◽  
Author(s):  
Michael Rudolph ◽  
J. Guillaume Pelletier ◽  
Denis Paré ◽  
Alain Destexhe
2004 ◽  
Vol 91 (6) ◽  
pp. 2884-2896 ◽  
Author(s):  
Michael Rudolph ◽  
Zuzanna Piwkowska ◽  
Mathilde Badoual ◽  
Thierry Bal ◽  
Alain Destexhe

In neocortical neurons, network activity can activate a large number of synaptic inputs, resulting in highly irregular subthreshold membrane potential ( Vm) fluctuations, commonly called “synaptic noise.” This activity contains information about the underlying network dynamics, but it is not easy to extract network properties from such complex and irregular activity. Here, we propose a method to estimate properties of network activity from intracellular recordings and test this method using theoretical and experimental approaches. The method is based on the analytic expression of the subthreshold Vm distribution at steady state in conductance-based models. Fitting this analytic expression to Vm distributions obtained from intracellular recordings provides estimates of the mean and variance of excitatory and inhibitory conductances. We test the accuracy of these estimates against computational models of increasing complexity. We also test the method using dynamic-clamp recordings of neocortical neurons in vitro. By using an on-line analysis procedure, we show that the measured conductances from spontaneous network activity can be used to re-create artificial states equivalent to real network activity. This approach should be applicable to intracellular recordings during different network states in vivo, providing a characterization of the global properties of synaptic conductances and possible insight into the underlying network mechanisms.


2005 ◽  
Vol 94 (4) ◽  
pp. 2805-2821 ◽  
Author(s):  
Michael Rudolph ◽  
Joe Guillaume Pelletier ◽  
Denis Paré ◽  
Alain Destexhe

The activation of the electroencephalogram (EEG) is paralleled with an increase in the firing rate of cortical neurons, but little is known concerning the conductance state of their membrane and its impact on their integrative properties. Here, we combined in vivo intracellular recordings with computational models to investigate EEG-activated states induced by stimulation of the brain stem ascending arousal system. Electrical stimulation of the pedonculopontine tegmental (PPT) nucleus produced long-lasting (≈20 s) periods of desynchronized EEG activity similar to the EEG of awake animals. Intracellularly, PPT stimulation locked the membrane into a depolarized state, similar to the up-states seen during deep anesthesia. During these EEG-activated states, however, the input resistance was higher than that during up-states. Conductance measurements were performed using different methods, which all indicate that EEG-activated states were associated with a synaptic activity dominated by inhibitory conductances. These results were confirmed by computational models of reconstructed pyramidal neurons constrained by the corresponding intracellular recordings. These models indicate that, during EEG-activated states, neocortical neurons are in a high-conductance state consistent with a stochastic integrative mode. The amplitude and timing of somatic excitatory postsynaptic potentials were nearly independent of the position of the synapses in dendrites, suggesting that EEG-activated states are compatible with coding paradigms involving the precise timing of synaptic events.


Neuroscience ◽  
2001 ◽  
Vol 107 (1) ◽  
pp. 13-24 ◽  
Author(s):  
A Destexhe ◽  
M Rudolph ◽  
J.-M Fellous ◽  
T.J Sejnowski

2014 ◽  
Vol 37 (2) ◽  
pp. 293-304 ◽  
Author(s):  
Man Yi Yim ◽  
Arvind Kumar ◽  
Ad Aertsen ◽  
Stefan Rotter

2014 ◽  
Vol 10 (1) ◽  
pp. 25-32 ◽  
Author(s):  
Andres De la Rossa ◽  
Denis Jabaudon

2004 ◽  
Vol 91 (5) ◽  
pp. 1990-1998 ◽  
Author(s):  
Pablo Fuentealba ◽  
Sylvain Crochet ◽  
Igor Timofeev ◽  
Mircea Steriade

To study the interactions between thalamic and cortical inputs onto neocortical neurons, we used paired-pulse stimulation (PPS) of thalamic and cortical inputs as well as PPS of two cortical or two thalamic inputs that converged, at different time intervals, onto intracellularly recorded cortical and thalamocortical neurons in anesthetized cats. PPS of homosynaptic cortico-cortical pathways produced facilitation, depression, or no significant effects in cortical pathways, whereas cortical responses to thalamocortical inputs were mostly facilitated at both short and long intervals. By contrast, heterosynaptic interactions between either cortical and thalamic, or thalamic and cortical, inputs generally produced decreases in the peak amplitudes and depolarization area of evoked excitatory postsynaptic potentials (EPSPs), with maximal effect at ∼10 ms and lasting from 60 to 100 ms. All neurons tested with thalamic followed by cortical stimuli showed a decrease in the apparent input resistance ( Rin), the time course of which paralleled that of decreased responses, suggesting that shunting is the factor accounting for EPSP's decrease. Only half of neurons tested with cortical followed by thalamic stimuli displayed changes in Rin. Spike shunting in the thalamus may account for those cases in which decreased synaptic responsiveness of cortical neurons was not associated with decreased Rin because thalamocortical neurons showed decreased firing probability during cortical stimulation. These results suggest a short-lasting but strong shunting between thalamocortical and cortical inputs onto cortical neurons.


2020 ◽  
Author(s):  
Marin Manuel

AbstractIntracellular recordings using sharp microelectrodes often rely on a technique called Discontinuous Current-Clamp to accurately record the membrane potential while injecting current through the same microelectrode. It is well known that a poor choice of DCC switching rate can lead to under-or over-estimation of the cell potential, however, its effect on the cell firing is rarely discussed. Here, we show that sub-optimal switching rates lead to an overestimation of cell excitability. We performed intracellular recordings of mouse spinal motoneurons and recorded their firing in response to pulses and ramps of current in Bridge and DCC mode at various switching rates. We demonstrate that using an incorrect (too low) DCC frequency leads not only to an underestimation of the input resistance, but also, paradoxically, to an artificial overestimation of the firing of these cells: neurons fire at lower current, and at higher frequencies than at higher DCC rates, or than the same neuron recorded in Bridge mode. These effects are dependent on the membrane time constant of the recorded cell, and special care needs to be taken in large cells with very short time constants. Our work highlights the importance of choosing an appropriate DCC switching rate to obtain not only accurate membrane potential readings but also an accurate representation of the firing of the cell.Significance StatementDiscontinuous Current-Clamp is a technique often used during intracellular recordings in vivo. However, incorrect usage of this technique can lead to incorrect interpretations. Poor choice of the DCC switching rate can lead to under- or over-estimation of the cell potential. In addition, we show here that sub-optimal switching rates lead to an overestimation of the cell excitability.


2013 ◽  
Vol 110 (1) ◽  
pp. 221-229 ◽  
Author(s):  
Jonathan Dilgen ◽  
Hugo A. Tejeda ◽  
Patricio O'Donnell

Although interactions between the amygdala and prefrontal cortex (PFC) are critical for emotional guidance of behavior, the manner in which amygdala affects PFC function is not clear. Whereas basolateral amygdala (BLA) output neurons exhibit many characteristics associated with excitatory neurotransmission, BLA stimulation typically inhibits PFC cell firing. This apparent discrepancy could be explained if local PFC inhibitory interneurons were activated by BLA inputs. Here, we used in vivo juxtacellular and intracellular recordings in anesthetized rats to investigate whether BLA inputs evoke feedforward inhibition in the PFC. Juxtacellular recordings revealed that BLA stimulation evoked action potentials in PFC interneurons and silenced most pyramidal neurons. Intracellular recordings from PFC pyramidal neurons showed depolarizing postsynaptic potentials, with multiple components evoked by BLA stimulation. These responses exhibited a relatively negative reversal potential (Erev), suggesting the contribution of a chloride component. Intracellular administration or pressure ejection of the GABA-A antagonist picrotoxin resulted in action-potential firing during the BLA-evoked response, which had a more depolarized Erev. These results suggest that BLA stimulation engages a powerful inhibitory mechanism within the PFC mediated by local circuit interneurons.


2018 ◽  
Author(s):  
Abed Ghanbari ◽  
Naixin Ren ◽  
Christian Keine ◽  
Carl Stoelzel ◽  
Bernhard Englitz ◽  
...  

AbstractInformation transmission in neural networks is influenced by both short-term synaptic plasticity (STP) as well as non-synaptic factors, such as after-hyperpolarization currents and changes in excitability. Although these effects have been widely characterized in vitro using intracellular recordings, how they interact in vivo is unclear. Here we develop a statistical model of the short-term dynamics of spike transmission that aims to disentangle the contributions of synaptic and non-synaptic effects based only on observed pre- and postsynaptic spiking. The model includes a dynamic functional connection with short-term plasticity as well as effects due to the recent history of postsynaptic spiking and slow changes in postsynaptic excitability. Using paired spike recordings, we find that the model accurately describes the short-term dynamics of in vivo spike transmission at a diverse set of identified and putative excitatory synapses, including a thalamothalamic connection in mouse, a thalamocortical connection in a female rabbit, and an auditory brainstem synapse in a female gerbil. We illustrate the utility of this modeling approach by showing how the spike transmission patterns captured by the model may be sufficient to account for stimulus-dependent differences in spike transmission in the auditory brainstem (endbulb of Held). Finally, we apply this model to large-scale multi-electrode recordings to illustrate how such an approach has the potential to reveal cell-type specific differences in spike transmission in vivo. Although short-term synaptic plasticity parameters estimated from ongoing pre- and postsynaptic spiking are highly uncertain, our results are partially consistent with previous intracellular observations in these synapses.Significance StatementAlthough synaptic dynamics have been extensively studied and modeled using intracellular recordings of post-synaptic currents and potentials, inferring synaptic effects from extracellular spiking is challenging. Whether or not a synaptic current contributes to postsynaptic spiking depends not only on the amplitude of the current, but also on many other factors, including the activity of other, typically unobserved, synapses, the overall excitability of the postsynaptic neuron, and how recently the postsynaptic neuron has spiked. Here we developed a model that, using only observations of pre- and postsynaptic spiking, aims to describe the dynamics of in vivo spike transmission by modeling both short-term synaptic plasticity and non-synaptic effects. This approach may provide a novel description of fast, structured changes in spike transmission.


2019 ◽  
Vol 325 ◽  
pp. 108324 ◽  
Author(s):  
Yonatan Katz ◽  
Michael Sokoletsky ◽  
Ilan Lampl

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