Emergence of dominant initiation sites for interictal spikes in rat neocortex.

Neuronal populations with unbalanced inhibition can generate interictal spikes (ISs), where each IS starts from a small initiation site and then spreads activation across a larger area. We used in vivo voltage-sensitive dye imaging to map the initiation site of ISs in rat visual cortex disinhibited by epidural application of bicuculline methiodide. Immediately after the application of bicuculline, the IS initiation sites were widely distributed over the entire disinhibited area. After ∼ 10 min, a small number of sites became "dominant" and initiated the majority of the ISs throughout the course of imaging. Such domination also occurred in cortical slices, which lack long-range connections between the cortex and subcortical structures. This domination of IS initiation sites may allow timing-related plasticity mechanisms to provide a spatial organization where connections projecting outward from the dominant initiation site become strengthened. Understanding the spatiotemporal organization of IS initiation sites may contribute to our understanding of epileptogenesis in its very early stages, because a dominant IS initiation site with strengthened outward connectivity may ultimately develop into a seizure focus.

Wave propagation of cortical population activity under urethane anesthesia is state dependent.

BACKGROUND: Propagating waves of excitation have been observed extensively in the neocortex, during both spontaneous and sensory-evoked activity, and they play a critical role in spatially organizing information processing. However, the state-dependence of these spatiotemporal propagation patterns is largely unexplored. In this report, we use voltage-sensitive dye imaging in the rat visual cortex to study the propagation of spontaneous population activity in two discrete cortical states induced by urethane anesthesia. RESULTS: While laminar current source density patterns of spontaneous population events in these two states indicate a considerable degree of similarity in laminar networks, lateral propagation in the more active desynchronized state is approximately 20% faster than in the slower synchronized state. Furthermore, trajectories of wave propagation exhibit a strong anisotropy, but the preferred direction is different depending on cortical state. CONCLUSIONS: Our results show that horizontal wave propagation of spontaneous neural activity is largely dependent on the global activity states of local cortical circuits.

Compression and reflection of visually evoked cortical waves.

Neuronal interactions between primary and secondary visual cortical areas are important for visual processing, but the spatiotemporal patterns of the interaction are not well understood. We used voltage-sensitive dye imaging to visualize neuronal activity in rat visual cortex and found visually evoked waves propagating from V1 to other visual areas. A primary wave originated in the monocular area of V1 and was "compressed" when propagating to V2. A reflected wave initiated after compression and propagated backward into V1. The compression occurred at the V1/V2 border, and local GABAA inhibition is important for the compression. The compression/reflection pattern provides a two-phase modulation: V1 is first depolarized by the primary wave, and then V1 and V2 are simultaneously depolarized by the reflected and primary waves, respectively. The compression/reflection pattern only occurred for evoked waves and not for spontaneous waves, suggesting that it is organized by an internal mechanism associated with visual processing.

An optically transparent multi-electrode array for combined electrophysiology and optophysiology at the mesoscopic scale.

OBJECTIVE: A number of tissue penetrating opto-electrodes to simultaneously record and optogenetically influence brain activity have been developed. For experiments at the surface of the brain, such as electrocorticogram (ECoG) recordings and surface optogenetics, fewer devices have been described and no device has found widespread adoption for neuroscientific experiments. One issue slowing adoption is the complexity and fragility of existing devices, typically based on transparent electrode materials like graphene and indium-tin oxide (ITO). We focused here on improving existing processes based on metal traces and polyimide (PI), which produce more robust and cost-effective devices, to develop a multi-electrode array for optophysiology. APPROACH: The most widely used substrate material for surface electrodes, PI, has seen little use for optophysiologicalµECoG/ECoG arrays. This is due to its lack of transparency at optogenetically relevant short wavelengths. Here we use very thin layers of PI in combination with chrome-gold-platinum electrodes to achieve the necessary substrate transparency and high mechanical flexibility in a device that still rejects light artifacts well. MAIN RESULTS: The manufactured surface arrays have a thickness of only 6.5 µm, resulting in 80% transparency for blue light. We demonstrate immunity against opto-electric artifacts, long term stability and biocompatibility as well as suitability for optical voltage imaging. The biocompatible arrays are capable of recording stable ECoGs over months without any measurable degradation and can be used to map the tonotopic organization of the curved rodent auditory cortex. SIGNIFICANCE: Our novel probes combine proven materials and processing steps to create optically near-transparent electrode arrays with superior longevity. In contrast to previous opto-electrodes, our probes are simple to manufacture, robust, offer long-term stability, and are a practical engineering solution for optophysiological experiments not requiring transparency of the electrode sites themselves.

Author Correction: Increasing neurogenesis refines hippocampal activity rejuvenating navigational learning strategies and contextual memory throughout life.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Increasing neurogenesis refines hippocampal activity rejuvenating navigational learning strategies and contextual memory throughout life.

Functional plasticity of the brain decreases during ageing causing marked deficits in contextual learning, allocentric navigation and episodic memory. Adult neurogenesis is a prime example of hippocampal plasticity promoting the contextualisation of information and dramatically decreases during ageing. We found that a genetically-driven expansion of neural stem cells by overexpression of the cell cycle regulators Cdk4/cyclinD1 compensated the age-related decline in neurogenesis. This triggered an overall inhibitory effect on the trisynaptic hippocampal circuit resulting in a changed profile of CA1 sharp-wave ripples known to underlie memory consolidation. Most importantly, increased neurogenesis rescued the age-related switch from hippocampal to striatal learning strategies by rescuing allocentric navigation and contextual memory. Our study demonstrates that critical aspects of hippocampal function can be reversed in old age, or compensated throughout life, by exploiting the brain's endogenous reserve of neural stem cells.

Crossmodal propagation of sensory-evoked and spontaneous activity in the rat neocortex.

In the cortex, neural responses to crossmodal stimulation are seen both in higher association areas and in primary sensory areas, and are thought to play a role in integration of crossmodal sensations. We used voltage-sensitive dye imaging (VSDI) to study the spatiotemporal characteristics of such crossmodal neural activity. We imaged three cortical regions in rat: primary visual cortex (V1), barrel field of primary somatosensory cortex (S1bf) and parietal association area (PA, flanked by V1 and S1bf). We find that sensory-evoked population activity can propagate in the form of a distinct propagating wave, robustly in either crossmodal direction. In single trials, the waveforms changed continuously during propagation, with dynamic variability from trial to trial, which we interpret as evidence for cortical involvement in the spreading process. To further characterize the functional anatomy of PA, we also studied the propagation of spontaneous sleep-like waves in this area. Using a novel flow-detection algorithm, we detected a propagation bias within PA of spontaneous waves--these tend to propagate parallel to the crossmodal axis, rather than orthogonal to it. Taken together, these findings demonstrate that intracortical networks show pre-attentive crossmodal propagation of activity, and suggest a potential mechanism for the establishment of crossmodal integration.

Measurement, modeling, and prediction of temperature rise due to optogenetic brain stimulation.

Optogenetics is one of the most important techniques in neurophysiology, with potential clinical applications. However, the strong light needed may cause harmful temperature rises. So far, there are no methods to reliably estimate brain heating and safe limits in actual optogenetic experiments. We used thermal imaging to directly measure such temperature rises at the surface of live mouse brains during laser illumination with wavelengths and intensities typical for optogenetics. We then modeled the temperature rise with a simple logarithmic model. Our results indicate that previous finite-element models can underestimate temperature increases by an order of magnitude. We validate our empirical model by predicting the temperature rise caused by pulsed stimulation paradigms. These predictions fit closely to the empirical data and constitute a better estimate of real temperature increases. Additionally, we provide a web-based app for easy calculation that can be used as a tool for safe design of optogenetic experiments.

Periodic Lateralized Epileptiform Discharges (PLEDs) in Patients With Neurosyphilis and HIV Infection.

Periodic lateralized epileptiform discharges (PLEDs) are an electroencephalographic pattern recorded in the setting of a variety of brain abnormalities. It is best recognized for its association with acute viral encephalitis, stroke, tumor, or latestatus epilepticus. However, there are other conditions that have been recognized as the underlying pathology for PLEDs such as alcohol withdrawal, Creutzfeldt-Jacob disease, anoxic brain injury, and hemiplegic migraine. However, there are only rare case reports of PLEDs in patients with neurosyphilis. Here, we report 2 patients presenting with encephalopathy and seizures with PLEDs, ipsilateral or contralateral to their main brain magnetic resonance imaging abnormalities. Further workup revealed neurosyphilis in both patients, one in association with human immunodeficiency virus (HIV) infection. Given the increasing incidence of neurosyphilis with or without HIV infection, these cases suggest neurosyphilis as a consideration in the differential for patients presenting with PLEDs.