Membrane Resonance in Pyramidal and GABAergic Neurons of the Mouse Perirhinal Cortex

The perirhinal cortex (PRC) is a polymodal associative region of the temporal lobe that works as a gateway between cortical areas and hippocampus. In recent years, an increasing interest arose in the role played by the PRC in learning and memory processes, such as object recognition memory, in contrast with certain forms of hippocampus-dependent spatial and episodic memory. The integrative properties of the PRC should provide all necessary resources to select and enhance the information to be propagated to and from the hippocampus. Among these properties, we explore in this paper the ability of the PRC neurons to amplify the output voltage to current input at selected frequencies, known as membrane resonance. Within cerebral circuits the resonance of a neuron operates as a filter toward inputs signals at certain frequencies to coordinate network activity in the brain by affecting the rate of neuronal firing and the precision of spike timing. Furthermore, the ability of the PRC neurons to resonate could have a fundamental role in generating subthreshold oscillations and in the selection of cortical inputs directed to the hippocampus. Here, performing whole-cell patch-clamp recordings from perirhinal pyramidal neurons and GABAergic interneurons of GAD67-GFP+ mice, we found, for the first time, that the majority of PRC neurons are resonant at their resting potential, with a resonance frequency of 0.5–1.5 Hz at 23°C and of 1.5–2.8 Hz at 36°C. In the presence of ZD7288 (blocker of HCN channels) resonance was abolished in both pyramidal neurons and interneurons, suggesting that Ih current is critically involved in resonance generation. Otherwise, application of TTx (voltage-dependent Na+ channel blocker) attenuates the resonance in pyramidal neurons but not in interneurons, suggesting that only in pyramidal neurons the persistent sodium current has an amplifying effect. These experimental results have also been confirmed by a computational model. From a functional point of view, the resonance in the PRC would affect the reverberating activity between neocortex and hippocampus, especially during slow wave sleep, and could be involved in the redistribution and strengthening of memory representation in cortical regions.

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Resonance with subthreshold oscillatory drive organizes activity and optimizes learning in neural networks

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1716933115 ◽

2018 ◽

Vol 115 (13) ◽

pp. E3017-E3025 ◽

Cited By ~ 11

Author(s):

James P. Roach ◽

Aleksandra Pidde ◽

Eitan Katz ◽

Jiaxing Wu ◽

Nicolette Ognjanovski ◽

...

Keyword(s):

Hippocampal Neurons ◽

External Input ◽

Neuronal Firing ◽

Network Activity ◽

Dependent Manner ◽

Information Encoding ◽

Subthreshold Oscillations ◽

Neuronal Network Model ◽

And Performance

Network oscillations across and within brain areas are critical for learning and performance of memory tasks. While a large amount of work has focused on the generation of neural oscillations, their effect on neuronal populations’ spiking activity and information encoding is less known. Here, we use computational modeling to demonstrate that a shift in resonance responses can interact with oscillating input to ensure that networks of neurons properly encode new information represented in external inputs to the weights of recurrent synaptic connections. Using a neuronal network model, we find that due to an input current-dependent shift in their resonance response, individual neurons in a network will arrange their phases of firing to represent varying strengths of their respective inputs. As networks encode information, neurons fire more synchronously, and this effect limits the extent to which further “learning” (in the form of changes in synaptic strength) can occur. We also demonstrate that sequential patterns of neuronal firing can be accurately stored in the network; these sequences are later reproduced without external input (in the context of subthreshold oscillations) in both the forward and reverse directions (as has been observed following learning in vivo). To test whether a similar mechanism could act in vivo, we show that periodic stimulation of hippocampal neurons coordinates network activity and functional connectivity in a frequency-dependent manner. We conclude that resonance with subthreshold oscillations provides a plausible network-level mechanism to accurately encode and retrieve information without overstrengthening connections between neurons.

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Knock-Down of Hippocampal DISC1 in Immune-Challenged Mice Impairs the Prefrontal–Hippocampal Coupling and the Cognitive Performance Throughout Development

Cerebral Cortex ◽

10.1093/cercor/bhaa291 ◽

2020 ◽

Author(s):

Xiaxia Xu ◽

Lingzhen Song ◽

Ileana L Hanganu-Opatz

Keyword(s):

Pyramidal Neurons ◽

Behavioral Assessment ◽

Neuronal Firing ◽

Network Activity ◽

Whole Brain ◽

Developmental Processes ◽

Knock Down ◽

Ca1 Pyramidal Neurons ◽

Local Circuits

Abstract Disrupted-in-schizophrenia 1 (DISC1) gene represents an intracellular hub of developmental processes. When combined with early environmental stressors, such as maternal immune activation, but not in the absence of thereof, whole-brain DISC1 knock-down leads to memory and executive deficits as result of impaired prefrontal–hippocampal communication throughout development. While synaptic dysfunction in neonatal prefrontal cortex (PFC) has been recently identified as one source of abnormal long-range coupling, the contribution of hippocampus (HP) is still unknown. Here, we aim to fill this knowledge gap by combining in vivo electrophysiology and optogenetics with morphological and behavioral assessment of immune-challenged mice with DISC1 knock-down either in the whole brain (GE) or restricted to pyramidal neurons in hippocampal CA1 area (GHPE). We found abnormal network activity, sharp-waves, and neuronal firing in CA1 that complement the deficits in upper layer of PFC. Moreover, optogenetic activating CA1 pyramidal neurons fails to activate the prefrontal local circuits. These deficits that persist till prejuvenile age relate to dendrite sparsification and loss of spines of CA1 pyramidal neurons. As a long-term consequence, DISC1 knock-down in HP leads to poorer recognition memory at prejuvenile age. Thus, DISC1-controlled developmental processes in HP in immune-challenged mice are critical for circuit function and cognitive behavior.

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Network resonance during slow-wave sleep facilitates memory consolidation through phase-coding

10.1101/565242 ◽

2019 ◽

Author(s):

Quinton M. Skilling ◽

Brittany C. Clawson ◽

Bolaji Eniwaye ◽

James Shaver ◽

Nicolette Ognjanovski ◽

...

Keyword(s):

Memory Consolidation ◽

Slow Wave Sleep ◽

Critical Role ◽

Spike Timing ◽

Network Activity ◽

Theta Band ◽

Phase Coding ◽

Neuronal Populations ◽

Network Oscillations ◽

Memory Representations

AbstractSleep plays a critical role in memory consolidation, however, the exact role that sleep and its effects on neural network dynamics play in this process is still unclear. Here, we combine computational and experimental approaches to study the dynamical, network-wide underpinnings of hippocampal memory consolidation during sleep. We provide data to support a novel hypothesis on the role of cellular resonance with sleep-associated theta band (4-12 Hz) hippocampal oscillations in this process. We show that increases in the stability of hippocampal memory representations after learning (which predicts successful memory consolidation) are mediated through emergent network-wide resonance and locking of neuronal activity to network oscillations. These changes arise in the network as a function of changes to network structure during learning, and mirror experimental findings in the hippocampus. Finally, we show that input-dependent pattern formation (e.g. “replay”) in the hippocampus during sleep states, together with spike timing dependent plasticity (STDP)-based memory consolidation, leads to universal network activity reorganization. This reorganization generates heterogeneous changes in neuronal spiking frequency, similar to what has been observed in a variety of brain circuits across periods of sleep. Our results support the hypothesis that sleep plays an active role in memory consolidation by switching the hippocampal network from rate-based to phase-based information representation. The mechanisms through which this occurs supports the integration of heterogeneous cell populations into memory traces.Significance StatementIn this study, we provide a mechanistic explanation of how sleep selectively facilitates memory consolidation, through recruitment of heterogeneous neuronal populations and structural reorganization of the network into an engram. Specifically, we show that emergent theta band oscillations during sleep facilitate stabilization of memory representations via spike timing dependent reinforcement. This stabilization, together with STDP, allows for systematic reorganization of synaptic connections within these populations, universally redistributing firing rates of participating neurons. Simultaneously, network oscillations facilitate a switch from rate-to phase-coding of information among neuronal populations with highly heterogenous firing frequencies, incorporating more neurons into the engram. Our results reconcile discrepant findings on network reorganization during sleep, and demonstrate a clear mechanism for both strengthening and weakening of synaptic efficacy during sleep.

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Rapid Temporal Modulation of Synchrony by Competition in Cortical Interneuron Networks

Neural Computation ◽

10.1162/089976604322742029 ◽

2004 ◽

Vol 16 (2) ◽

pp. 251-275 ◽

Cited By ~ 76

Author(s):

P.H.E. Tiesinga ◽

T. J. Sejnowski

Keyword(s):

Cortical Neurons ◽

Pyramidal Neurons ◽

Background Activity ◽

Pyramidal Cells ◽

Spike Timing ◽

Network Activity ◽

Local Networks ◽

Rapid Changes ◽

Asynchronous State ◽

The Impact

The synchrony of neurons in extrastriate visual cortex is modulated by selective attention even when there are only small changes in firing rate (Fries, Reynolds, Rorie, & Desimone, 2001). We used Hodgkin-Huxley type models of cortical neurons to investigate the mechanism by which the degree of synchrony can be modulated independently of changes in firing rates. The synchrony of local networks of model cortical interneurons interacting through GABAA synapses was modulated on a fast timescale by selectively activating a fraction of the interneurons. The activated interneurons became rapidly synchronized and suppressed the activity of the other neurons in the network but only if the network was in a restricted range of balanced synaptic background activity. During stronger background activity, the network did not synchronize, and for weaker background activity, the network synchronized but did not return to an asynchronous state after synchronizing. The inhibitory output of the network blocked the activity of pyramidal neurons during asynchronous network activity, and during synchronous network activity, it enhanced the impact of the stimulus-related activity of pyramidal cells on receiving cortical areas (Salinas & Sejnowski, 2001). Synchrony by competition provides a mechanism for controlling synchrony with minor alterations in rate, which could be useful for information processing. Because traditional methods such as cross-correlation and the spike field coherence require several hundred milliseconds of recordings and cannot measure rapid changes in the degree of synchrony, we introduced a new method to detect rapid changes in the degree of coincidence and precision of spike timing.

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Faculty Opinions recommendation of Differential Control of Axonal and Somatic Resting Potential by Voltage-Dependent Conductances in Cortical Layer 5 Pyramidal Neurons.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.732809725.793574922 ◽

2020 ◽

Author(s):

Vitaly Klyachko

Keyword(s):

Pyramidal Neurons ◽

Cortical Layer ◽

Resting Potential ◽

Voltage Dependent ◽

Differential Control

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Dynamic modulation of spike timing-dependent calcium influx during corticostriatal upstates

Journal of Neurophysiology ◽

10.1152/jn.00232.2013 ◽

2013 ◽

Vol 110 (7) ◽

pp. 1631-1645 ◽

Cited By ~ 13

Author(s):

R. C. Evans ◽

Y. M. Maniar ◽

K. T. Blackwell

Keyword(s):

Synaptic Plasticity ◽

Slow Wave Sleep ◽

Calcium Influx ◽

Spike Timing ◽

Medium Spiny Neuron ◽

Calcium Transients ◽

Biophysical Model ◽

Published Data ◽

High Calcium

The striatum of the basal ganglia demonstrates distinctive upstate and downstate membrane potential oscillations during slow-wave sleep and under anesthetic. The upstates generate calcium transients in the dendrites, and the amplitude of these calcium transients depends strongly on the timing of the action potential (AP) within the upstate. Calcium is essential for synaptic plasticity in the striatum, and these large calcium transients during the upstates may control which synapses undergo plastic changes. To investigate the mechanisms that underlie the relationship between calcium and AP timing, we have developed a realistic biophysical model of a medium spiny neuron (MSN). We have implemented sophisticated calcium dynamics including calcium diffusion, buffering, and pump extrusion, which accurately replicate published data. Using this model, we found that either the slow inactivation of dendritic sodium channels (NaSI) or the calcium inactivation of voltage-gated calcium channels (CDI) can cause high calcium corresponding to early APs and lower calcium corresponding to later APs. We found that only CDI can account for the experimental observation that sensitivity to AP timing is dependent on NMDA receptors. Additional simulations demonstrated a mechanism by which MSNs can dynamically modulate their sensitivity to AP timing and show that sensitivity to specifically timed pre- and postsynaptic pairings (as in spike timing-dependent plasticity protocols) is altered by the timing of the pairing within the upstate. These findings have implications for synaptic plasticity in vivo during sleep when the upstate-downstate pattern is prominent in the striatum.

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Effect of Common Anesthetics on Dendritic Properties in Layer 5 Neocortical Pyramidal Neurons

Journal of Neurophysiology ◽

10.1152/jn.01126.2007 ◽

2008 ◽

Vol 99 (3) ◽

pp. 1394-1407 ◽

Cited By ~ 28

Author(s):

Sarah Potez ◽

Matthew E. Larkum

Keyword(s):

High Frequency ◽

Pyramidal Neurons ◽

Animal Experiments ◽

Apical Dendrite ◽

Network Activity ◽

Calcium Spikes ◽

Firing Properties ◽

The Impact

Understanding the impact of active dendritic properties on network activity in vivo has so far been restricted to studies in anesthetized animals. However, to date no study has been made to determine the direct effect of the anesthetics themselves on dendritic properties. Here, we investigated the effects of three types of anesthetics commonly used for animal experiments (urethane, pentobarbital and ketamine/xylazine). We investigated the generation of calcium spikes, the propagation of action potentials (APs) along the apical dendrite and the somatic firing properties in the presence of anesthetics in vitro using dual somatodendritic whole cell recordings. Calcium spikes were evoked with dendritic current injection and high-frequency trains of APs at the soma. Surprisingly, we found that the direct actions of anesthetics on calcium spikes were very different. Two anesthetics (urethane and pentobarbital) suppressed dendritic calcium spikes in vitro, whereas a mixture of ketamine and xylazine enhanced them. Propagation of spikes along the dendrite was not significantly affected by any of the anesthetics but there were various changes in somatic firing properties that were highly dependent on the anesthetic. Last, we examined the effects of anesthetics on calcium spike initiation and duration in vivo using high-frequency trains of APs generated at the cell body. We found the same anesthetic-dependent direct effects in addition to an overall reduction in dendritic excitability in anesthetized rats with all three anesthetics compared with the slice preparation.

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Dichotomy of Action-Potential Backpropagation in CA1 Pyramidal Neuron Dendrites

Journal of Neurophysiology ◽

10.1152/jn.2001.86.6.2998 ◽

2001 ◽

Vol 86 (6) ◽

pp. 2998-3010 ◽

Cited By ~ 119

Author(s):

Nace L. Golding ◽

William L. Kath ◽

Nelson Spruston

Keyword(s):

Action Potential ◽

Action Potentials ◽

Pyramidal Neurons ◽

Synaptic Activity ◽

Resting Potential ◽

Model Parameters ◽

Voltage Sensitivity ◽

Whole Cell ◽

Ca1 Pyramidal Neurons ◽

Whole Cell Recordings

In hippocampal CA1 pyramidal neurons, action potentials are typically initiated in the axon and backpropagate into the dendrites, shaping the integration of synaptic activity and influencing the induction of synaptic plasticity. Despite previous reports describing action-potential propagation in the proximal apical dendrites, the extent to which action potentials invade the distal dendrites of CA1 pyramidal neurons remains controversial. Using paired somatic and dendritic whole cell recordings, we find that in the dendrites proximal to 280 μm from the soma, single backpropagating action potentials exhibit <50% attenuation from their amplitude in the soma. However, in dendritic recordings distal to 300 μm from the soma, action potentials in most cells backpropagated either strongly (26–42% attenuation; n = 9/20) or weakly (71–87% attenuation; n = 10/20) with only one cell exhibiting an intermediate value (45% attenuation). In experiments combining dual somatic and dendritic whole cell recordings with calcium imaging, the amount of calcium influx triggered by backpropagating action potentials was correlated with the extent of action-potential invasion of the distal dendrites. Quantitative morphometric analyses revealed that the dichotomy in action-potential backpropagation occurred in the presence of only subtle differences in either the diameter of the primary apical dendrite or branching pattern. In addition, action-potential backpropagation was not dependent on a number of electrophysiological parameters (input resistance, resting potential, voltage sensitivity of dendritic spike amplitude). There was, however, a striking correlation of the shape of the action potential at the soma with its amplitude in the dendrite; larger, faster-rising, and narrower somatic action potentials exhibited more attenuation in the distal dendrites (300–410 μm from the soma). Simple compartmental models of CA1 pyramidal neurons revealed that a dichotomy in action-potential backpropagation could be generated in response to subtle manipulations of the distribution of either sodium or potassium channels in the dendrites. Backpropagation efficacy could also be influenced by local alterations in dendritic side branches, but these effects were highly sensitive to model parameters. Based on these findings, we hypothesize that the observed dichotomy in dendritic action-potential amplitude is conferred primarily by differences in the distribution, density, or modulatory state of voltage-gated channels along the somatodendritic axis.

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