University of Alberta

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BOSC: a better oscillation detection method, extracts both sustained and transient rhythms from rat hippocampal recordings

PMID: 21997899

Hughes AM, Whitten TA, Caplan JB, Dickson CT

Hippocampus 2012 Jun;22(6):1417-28

Abstract

Neuronal population oscillations at a variety of frequencies can be readily seen in electroencephalographic (EEG) as well as local field potential recordings in many different species. Although these brain rhythms have been studied for many years, the methods for identifying discrete oscillatory epochs are still widely variable across studies. The “better oscillation detection” (BOSC) method applies standardized criteria to detect runs of “true” oscillatory activity and rejects transient events that do not reflect actual rhythms. It does so by estimating the background spectrum of the actual signal to derive detection criteria that include both power and duration thresholds. This method has not yet been applied to nonhuman data. Here, we test the BOSC method on two important rat hippocampal oscillatory signals, the theta rhythm and slow oscillation (SO), two large amplitude and mutually exclusive states. The BOSC method detected both the relatively sustained theta rhythm and the relatively transient SO apparent under urethane anesthesia and was relatively resilient to spectral features that changed across states, complementing previous findings for human EEG. Detection of oscillatory activity using the BOSC method (but not more traditional Fourier transform-based power analysis) corresponded well with human expert ratings. Moreover, for near-continuous theta, BOSC proved useful for detecting discrete disruptions that were associated with sudden and large amplitude phase shifts of the ongoing rhythm. Thus, the BOSC method accurately extracts oscillatory and nonoscillatory episodes from field potential recordings and produces systematic, objective, and consistent results-not only across frequencies, brain regions, tasks, and waking states, as shown previously, but also across species and for both sustained and transient rhythms. Thus, the BOSC method will facilitate more direct comparisons of oscillatory brain activity across all types of experimental paradigms.

Neurosilence: profound suppression of neural activity following intracerebral administration of the protein synthesis inhibitor anisomycin

PMID: 22396412

Sharma AV, Nargang FE, Dickson CT

J. Neurosci. 2012 Feb;32(7):2377-87

Abstract

Early in their formation, memories are thought to be labile, requiring a process called consolidation to give them near-permanent stability. Evidence for consolidation as an active and biologically separate mnemonic process has been established through posttraining manipulations of the brain that promote or disrupt subsequent retrieval. Consolidation is thought to be ultimately mediated via protein synthesis since translational inhibitors such as anisomycin disrupt subsequent memory when administered in a critical time window just following initial learning. However, when applied intracerebrally, they may induce additional neural disturbances. Here, we report that intrahippocampal microinfusions of anisomycin in urethane-anesthetized rats at dosages previously used in memory consolidation studies strongly suppressed (and in some cases abolished) spontaneous and evoked local field potentials (and associated extracellular current flow) as well as multiunit activity. These effects were not coupled to the production of pathological electrographic activity nor were they due to cell death. However, the amount of suppression was correlated with the degree of protein synthesis inhibition as measured by autoradiography and was also observed with cycloheximide, another translational inhibitor. Our results suggest that (1) the amnestic effects of protein synthesis inhibitors are confounded by neural silencing and that (2) intact protein synthesis is crucial for neural signaling itself.

A critical test of the hippocampal theta model of anxiolytic drug action

PMID: 21723303

Yeung M, Treit D, Dickson CT

Neuropharmacology 2012 Jan;62(1):155-60

Abstract

Hippocampal theta rhythms have been associated with a number of behavioural processes, including learning, memory and arousal. Recently it has been argued that the suppression of hippocampal theta is a valid indicator of anxiolytic drug action. Like all such models, however, it has relied almost exclusively on the experimental effects of well-known, clinically proven anxiolytic compounds for validation. The actual predictive validity of putative models of anxiolytic drug action, however, cannot be rigorously tested with this approach alone. The present study provides a stringent test of the predictive validity of the theta suppression model, using the drug phenytoin (50 mg/kg and 10 mg/kg), and a positive comparison compound, diazepam (2 mg/kg). Phenytoin has two important properties that are advantageous for assessing the validity of the theta suppression model: 1) it is a standard antiepileptic drug with no known anxiolytic effects, and 2) its primary mechanism of action is through suppression of the persistent sodium current, an effect that should also suppress hippocampal theta. Because of the latter property, we also directly compared the effects of phenytoin in the theta suppression model with its effects in the most widely tested behavioural model of anxiolytic drug action, the elevated plus-maze. While an anxiolytic-like effect of phenytoin in the theta suppression model might be expected simply due to its suppressive effects on sodium channel currents, anxiolytic effects in both tests would provide strong support for the predictive validity of the theta suppression model. Surprisingly, phenytoin produced clear anxiolytic-like effects in both neurophysiological and behavioural models, thus providing strong evidence of the predictive validity of the theta suppression model. This article is part of a Special Issue entitled ‘Anxiety and Depression’.

Active expiration induced by excitation of ventral medulla in adult anesthetized rats

PMID: 21414911

Pagliardini S, Janczewski WA, Tan W, Dickson CT, Deisseroth K, Feldman JL

J. Neurosci. 2011 Feb;31(8):2895-905

Abstract

Data from perinatal and juvenile rodents support our hypothesis that the preBötzinger complex generates inspiratory rhythm and the retrotrapezoid nucleus-parafacial respiratory group (RTN/pFRG) generates active expiration (AE). Although the role of the RTN/pFRG in adulthood is disputed, we hypothesized that its rhythmogenicity persists but is typically silenced by synaptic inhibition. We show in adult anesthetized rats that local pharmacological disinhibition or optogenetic excitation of the RTN/pFRG can generate AE and transforms previously silent RTN/pFRG neurons into rhythmically active cells whose firing is correlated with late-phase active expiration. Brief excitatory stimuli also reset the respiratory rhythm, indicating strong coupling of AE to inspiration. The AE network location in adult rats overlaps with the perinatal pFRG and appears lateral to the chemosensitive region of adult RTN. We suggest that (1) the RTN/pFRG contains a conditional oscillator that generates AE, and (2) at rest and in anesthesia, synaptic inhibition of RTN/pFRG suppresses AE.

A better oscillation detection method robustly extracts EEG rhythms across brain state changes: the human alpha rhythm as a test case

PMID: 20807577

Whitten TA, Hughes AM, Dickson CT, Caplan JB

Neuroimage 2011 Jan;54(2):860-74

Abstract

Oscillatory activity is a principal mode of operation in the brain. Despite an intense resurgence of interest in the mechanisms and functions of brain rhythms, methods for the detection and analysis of oscillatory activity in neurophysiological recordings are still highly variable across studies. We recently proposed a method for detecting oscillatory activity from time series data, which we call the BOSC (Better OSCillation detection) method. This method produces systematic, objective, and consistent results across frequencies, brain regions and tasks. It does so by modeling the functional form of the background spectrum by fitting the empirically observed spectrum at the recording site. This minimizes bias in oscillation detection across frequency, region and task. Here we show that the method is also robust to dramatic changes in state that are known to influence the shape of the power spectrum, namely, the presence versus absence of the alpha rhythm, and can be applied to independent components, which are thought to reflect underlying sources, in addition to individual raw signals. This suggests that the BOSC method is an effective tool for measuring changes in rhythmic activity in the more common research scenario wherein state is unknown.

Ups and downs in the hippocampus: the influence of oscillatory sleep states on “neuroplasticity” at different time scales

PMID: 20394778

Dickson CT

Behav. Brain Res. 2010 Dec;214(1):35-41

Abstract

Spontaneous state-dependent oscillatory dynamics in the brain are relevant to both ongoing and prospective neural and behavioural function. In the hippocampus, the presence of different patterns of coordinated network activity during offline (sleep) states has the potential to modify neural connections and thus influence memory storage. In addition to theta (3-12Hz) and ripple (100-300Hz) activity, the hippocampus also demonstrates a slow oscillation (SO: < or =1Hz) during sleep which prominently organizes hippocampal cellular activity and dynamically coordinates ensembles across the entire forebrain into temporal frames of activity (UP) and inactivity (DOWN). The SO also significantly modulates hippocampal excitatory synaptic transmission on both a short (within cycle) and medium (across state) time scale and through its dynamic coordination with neocortical areas has the potential to function as a platform for long-term bidirectional synaptic plasticity. Recent evidence suggests that it is of direct benefit for the consolidation of hippocampal-dependent memories and thus, further investigation of its mechanisms in modulating short-to-long-term neural plasticity is certainly warranted.

Short-duration epileptic discharges show a distinct phase preference during ongoing hippocampal slow oscillations

PMID: 20719925

de Guzman PH, Nazer F, Dickson CT

J. Neurophysiol. 2010 Oct;104(4):2194-202

Abstract

Non-REM (slow-wave) sleep has been shown to facilitate temporal lobe epileptiform events, whereas REM sleep seems more restrictive. This state-dependent modulation may be the result of the enhancement of excitatory synaptic transmission and/or the degree of network synchronization expressed within the hippocampus of the temporal lobe. The slow oscillation (SO), a ∼1 Hz oscillatory pattern expressed during non-REM sleep and urethane anesthesia, has been recently shown to facilitate the generation, maintenance, and propagation of stimulus-evoked epileptiform activity in the hippocampus. To further address the state-dependent modulation of epileptic activity during the SO, we studied the properties of short-duration interictal-like activity generated by focal application of penicillin in the hippocampus of urethane-anesthetized rats. Epileptiform spikes were larger but only slightly more prevalent during the SO as opposed to the theta (REM-like) state. More notably, however, epileptic spikes had a significant tendency to occur just following the peak negativity of ongoing SO cycles. Because of the known phase-dependent changes in 1) synaptic excitability (just following the positive peak of the SO) and 2) network synchronization (during the negative peak of the SO), these results suggest that it is the synchrony and not the changes in synaptic excitability that lead to the facilitation of epileptiform activity during sleep-like slow wave states.

Changes in hippocampal excitatory synaptic transmission during cholinergically induced theta and slow oscillation states

PMID: 19437417

Schall KP, Dickson CT

Hippocampus 2010 Feb;20(2):279-92

Abstract

Neural processing in the hippocampus (HPC) during sleep is important for declarative memory storage. Previously, we have shown that alternations of sleep-like REM and non-REM brain states that involve changing patterns of synchronized oscillatory network activity in the HPC [i.e., theta and the slow oscillation (SO), respectively] robustly and differentially influence excitatory synaptic transmission in a variety of hippocampal pathways. Given that state in the HPC is dependent on variations in cholinergic tone in both sleep and under urethane anesthesia, in the present study we induced theta and SO states via systemic cholinergic manipulations in urethane-anesthetized rats to confirm similar changes in synaptic responsiveness. This was conducted using linear multiprobe recordings and current source density analysis of electrically evoked potentials in commissural and temporal ammonic inputs to CA1 and medial and lateral perforant path inputs to dentate gyrus (DG). Cholinergic agonism and antagonism induced theta and the SO, respectively, and similarly to the case with spontaneous states, also diminished and promoted, respectively, excitatory synaptic currents in all pathways (except for the medial perforant path input to DG which showed the opposite modulation). These results suggest that both state and cholinergic tone bias the hippocampal network during natural sleep across REM and non-REM episodes and that this modulation may play an important role in the consolidation of declarative memories.

Rats’ use of geometric, featural and orientation cues to locate a hidden goal

PMID: 19683037

Batty ER, Hoban L, Spetch ML, Dickson CT

Behav. Processes 2009 Nov;82(3):327-34

Abstract

Over the past 20 years, a great deal of research has examined how different animals can use the geometric properties of the environment to determine their heading. Less well studied is how rats use the geometric properties of an environment to navigate, or determine the location, when it is not necessary to establish heading. Specifically, it is unclear to what extent rats still rely on geometric cues when they are not disoriented. In the current study, rats were trained to find food in one corner of a rectangular environment under either oriented or disoriented conditions. Probe tests placed geometric, featural and orientation cues in conflict. Results showed that featural cues exerted little control over the rats’ search preferences. All rats, whether trained while oriented or trained while disoriented, used geometric cues when these were the only cues available. Rats trained in the disoriented condition preferred geometric cues to orientation cues, whereas rats trained in the oriented condition showed more equal preference for orientation and geometric cues.

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