Entorhinal cortex lesions result in adenosine-sensitive high frequency oscillations in the hippocampus

Ortiz, Franco; Gutiérrez, Rafael

doi:10.1016/j.expneurol.2015.06.009

Cited by 10 publications

(11 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This model requires a lesion in the entorhinal cortex in situ, before removal of the brain, which disrupts corticocortical and cortico-hippocampal connections producing an activity-dependent functional disinhibition of the hippocam-pus. This results in typical FRs in subsequently recorded brain slices (Ortiz and Gutiérrez, 2015).…”

Section: Introductionmentioning

confidence: 72%

Early Appearance and Spread of Fast Ripples in the Hippocampus in a Model of Cortical Traumatic Brain Injury

et al. 2018

Self Cite

View full text Add to dashboard Cite

Fast ripples (FRs; activity of >250 Hz) have been considered as a biomarker of epileptic activity in the hippocampus and entorhinal cortex; it is thought that they signal the focus of seizure generation. Similar high-frequency network activity has been produced by changing extracellular medium composition, by using pro-epileptic substances, or by electrical stimulation. Here we study the propagation of these events between different subregions of the male rat hippocampus in a recently introduced experimental model of FRs in entorhinal cortex-hippocampal slices By using a matrix of 4096 microelectrodes, the sites of initiation, propagation pathways, and spatiotemporal characteristics of activity patterns could be studied with unprecedented high resolution. To this end, we developed an analytic tool based on bidimensional current source density estimation, which delimits sinks and sources with a high precision and evaluates their trajectories using the concept of center of mass. With this methodology, we found that FRs can arise almost simultaneously at noncontiguous sites in the CA3-to-CA1 direction, underlying the spatial heterogeneity of epileptogenic foci, while continuous somatodendritic waves of activity develop. An unexpected, yet important propagation route is the propagation of activity from CA3 into the hilus and dentate gyrus. This pathway may cause reverberating activation of both regions, supporting sustained pathological network events and altered information processing in hippocampal networks. Fast ripples (FRs) have been considered as a biomarker of epileptic activity and may signal the focus of seizure generation. In a model of traumatic brain injury in the rat, FRs appear in the hippocampus within a couple of hours after an extrahippocampal, cortical lesion. We analyzed the origin and dynamics of the FRs in the hippocampus using massive electrophysiological recordings, allowing an unprecedented high spatiotemporal resolution. We show that FRs originate in distinct and noncontiguous locations within the CA3 region and uncover, with high precision, the extent and dynamics of their current density. This activity propagates toward CA1 but also backpropagates to the hilus and the dentate gyrus, suggesting activation of defined microcircuits that can sustain recurrent excitation.

show abstract

Section: Introductionmentioning

confidence: 72%

Early Appearance and Spread of Fast Ripples in the Hippocampus in a Model of Cortical Traumatic Brain Injury

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…Second, we hypothesize that injury to efferent axonal projections from the hippocampus (via the fornix, for example) may disrupt the transmission of ripple-associated relay events to the neocortex, leading to impairment of memory re-distribution. Third, we hypothesize that widespread loss of synaptic input into the hippocampus (e.g., entorhinal projections) due to axonal injury could inappropriately bias the hippocampus towards its deafferented, synchronous state, the SPW-R state, which is further supported by a recent set of experiments demonstrating pathological high frequency activity after perforant path disruption (Ortiz and Gutiérrez, 2015 ). This could potentially cause widespread memory formation and consolidation difficulties, sleep cycle disturbance, and epileptiform activity, all symptoms classically observed after TBI.…”

Section: Timing Deficits In Hippocampal Network Hypothesized As Mechmentioning

confidence: 65%

Disruption of Network Synchrony and Cognitive Dysfunction After Traumatic Brain Injury

Wolf

Koch

2016

Front. Syst. Neurosci.

View full text Add to dashboard Cite

Traumatic brain injury (TBI) is a heterogeneous disorder with many factors contributing to a spectrum of severity, leading to cognitive dysfunction that may last for many years after injury. Injury to axons in the white matter, which are preferentially vulnerable to biomechanical forces, is prevalent in many TBIs. Unlike focal injury to a discrete brain region, axonal injury is fundamentally an injury to the substrate by which networks of the brain communicate with one another. The brain is envisioned as a series of dynamic, interconnected networks that communicate via long axonal conduits termed the “connectome”. Ensembles of neurons communicate via these pathways and encode information within and between brain regions in ways that are timing dependent. Our central hypothesis is that traumatic injury to axons may disrupt the exquisite timing of neuronal communication within and between brain networks, and that this may underlie aspects of post-TBI cognitive dysfunction. With a better understanding of how highly interconnected networks of neurons communicate with one another in important cognitive regions such as the limbic system, and how disruption of this communication occurs during injury, we can identify new therapeutic targets to restore lost function. This requires the tools of systems neuroscience, including electrophysiological analysis of ensemble neuronal activity and circuitry changes in awake animals after TBI, as well as computational modeling of the effects of TBI on these networks. As more is revealed about how inter-regional neuronal interactions are disrupted, treatments directly targeting these dysfunctional pathways using neuromodulation can be developed.

show abstract

“…Besides biochemical and behavioral alternations after TBI induction, changes in neuronal activity may also play a role in the consequences of TBI. Electrophysiological studies demonstrated that changes in the excitability of the hippocampal circuit occur after TBI (Ortiz & Gutiérrez, 2015;Witgen et al, 2005). Additionally, TBI is associated with neuronal cell loss (Witgen et al, 2005), modification in cellular homeostasis (D'Ambrosio, Maris, Grady, Winn, & Janigro, 1999) and changes in synaptic transmission (Toth et al, 1997) and alterations in firing patterns in different hippocampal areas (Witgen et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Enhancement of intrinsic neuronal excitability‐mediated by a reduction in hyperpolarization‐activated cation current (I_h) in hippocampal CA1 neurons in a rat model of traumatic brain injury

et al. 2020

View full text Add to dashboard Cite

Traumatic brain injury (TBI) is associated with epileptiform activity in the hippocampus; however, the underlying mechanisms have not been fully determined. The goal was to understand what changes take place in intrinsic neuronal physiology in the hippocampus after blunt force trauma to the cortex. In this context, hyperpolarization-activated cation current (I h) currents may have a critical role in modulating the neuronal intrinsic membrane excitability; therefore, its contribution to the TBI-induced hyperexcitability was assessed. In a model of TBI caused by controlled cortical impact (CCI), the intrinsic electrophysiological properties of pyramidal neurons were examined 1 week after TBI induction in rats. Whole-cell patch-clamp recordings were performed under current-and voltage-clamp conditions following ionotropic receptors blockade. Induction of TBI caused changes in the intrinsic excitability of pyramidal neurons, as shown by a significant increase and decrease in firing frequency and in the rheobase current, respectively (p < .05). The evoked firing rate and the action potential time to peak were also significantly increased and decreased, respectively (p < .05). In the TBI group, the amplitude of instantaneous and steadystate I h currents was both significantly smaller than those in the control group (p < .05). The I h current density was also significantly decreased (p < .001). Findings indicated that TBI led to an increase in the intrinsic excitability in CA1 pyramidal neurons and changes in I h current could be, in part, one of the underlying mechanisms involved in this hyperexcitability.

show abstract

Entorhinal cortex lesions result in adenosine-sensitive high frequency oscillations in the hippocampus

Cited by 10 publications

References 50 publications

Early Appearance and Spread of Fast Ripples in the Hippocampus in a Model of Cortical Traumatic Brain Injury

Early Appearance and Spread of Fast Ripples in the Hippocampus in a Model of Cortical Traumatic Brain Injury

Disruption of Network Synchrony and Cognitive Dysfunction After Traumatic Brain Injury

Enhancement of intrinsic neuronal excitability‐mediated by a reduction in hyperpolarization‐activated cation current (I_h) in hippocampal CA1 neurons in a rat model of traumatic brain injury

Contact Info

Product

Resources

About

Entorhinal cortex lesions result in adenosine-sensitive high frequency oscillations in the hippocampus

Cited by 10 publications

References 50 publications

Early Appearance and Spread of Fast Ripples in the Hippocampus in a Model of Cortical Traumatic Brain Injury

Early Appearance and Spread of Fast Ripples in the Hippocampus in a Model of Cortical Traumatic Brain Injury

Disruption of Network Synchrony and Cognitive Dysfunction After Traumatic Brain Injury

Enhancement of intrinsic neuronal excitability‐mediated by a reduction in hyperpolarization‐activated cation current (Ih) in hippocampal CA1 neurons in a rat model of traumatic brain injury

Contact Info

Product

Resources

About

Enhancement of intrinsic neuronal excitability‐mediated by a reduction in hyperpolarization‐activated cation current (I_h) in hippocampal CA1 neurons in a rat model of traumatic brain injury