Exposure to behaviourally relevant odour reveals differential characteristics in rat central olfactory pathways as studied through oscillatory activities

This study investigated how changes in nutritional motivation modulate odour-related oscillatory activities at several levels of the olfactory pathway in non-trained rats. Local field potential recordings were obtained in freely moving animals in the olfactory bulb (OB), anterior and posterior parts of the piriform cortex (APC and PPC respectively) and lateral entorhinal cortex (EC). Dynamic signal analysis detected changes in power during odour presentation for several frequency bands The results showed that in most cases odour presentation was associated with changes in a wide 15-90 Hz frequency band of activity in each olfactory structure. However, nutritional state modulated initial responses to food odour (FO) in the OB and EC selectively in the 15-30 Hz frequency band. Changes in nutritional state also modulated responses to repeated FO stimuli. Habituation was expressed differentially across structures with a clear dissociation between the two parts of the piriform cortex. Finally, systemic injections of scopolamine (0.125 mg/kg) selectively blocked expression of the nutritional modulation in the OB found in the beta band. These results suggest that internal state can differentially modulate odour processing among different olfactory areas and point to a cholinergic-sensitive beta band oscillation during presentation of a behaviourally meaningful odorant.     

Brain Activity at 70–80 Hz Changes during Olfactory Stimulation Protocols in Drosophila

Oscillatory and synchronized activities in the mammalian brain have been correlated with the execution of complex cognitive tasks. Similar oscillations have been observed in local field potentials (LFPs) in flies, in this case correlated with different attentional states. To further test the significance of these oscillations we recorded LFPs from the brain of Drosophila melanogaster as it responded to the presentation of olfactory stimuli. We find that responses in the 70–80 Hz range increase during olfactory stimulation. Recurrent stimulation specifically decreased the power of LFPs in this frequency range. Delivery of electric shocks before olfactory stimulation modulated LFPs in the 70–80 Hz range by evoking a transient increase. These results suggest that these signals are a simple neuronal correlate of higher-order olfactory processing in flies.     

Ketamine-induced oscillations in the motor circuit of the rat basal ganglia

Oscillatory activity can be widely recorded in the cortex and basal ganglia. This activity may play a role not only in the physiology of movement, perception and cognition, but also in the pathophysiology of psychiatric and neurological diseases like schizophrenia or Parkinson's disease. Ketamine administration has been shown to cause an increase in gamma activity in cortical and subcortical structures, and an increase in 150 Hz oscillations in the nucleus accumbens in healthy rats, together with hyperlocomotion.We recorded local field potentials from motor cortex, caudate-putamen (CPU), substantia nigra pars reticulata (SNr) and subthalamic nucleus (STN) in 20 awake rats before and after the administration of ketamine at three different subanesthetic doses (10, 25 and 50 mg/Kg), and saline as control condition. Motor behavior was semiautomatically quantified by custom-made software specifically developed for this setting.Ketamine induced coherent oscillations in low gamma (~ 50 Hz), high gamma (~ 80 Hz) and high frequency (HFO, ~ 150 Hz) bands, with different behavior in the four structures studied. While oscillatory activity at these three peaks was widespread across all structures, interactions showed a different pattern for each frequency band. Imaginary coherence at 150 Hz was maximum between motor cortex and the different basal ganglia nuclei, while low gamma coherence connected motor cortex with CPU and high gamma coherence was more constrained to the basal ganglia nuclei. Power at three bands correlated with the motor activity of the animal, but only coherence values in the HFO and high gamma range correlated with movement. Interactions in the low gamma band did not show a direct relationship to movement.These results suggest that the motor effects of ketamine administration may be primarily mediated by the induction of coherent widespread high-frequency activity in the motor circuit of the basal ganglia, together with a frequency-specific pattern of connectivity among the structures analyzed.     

Oscillatory synchrony and human visual cognition.

Oscillatory synchrony could be used to establish dynamic links between the various cortical areas participating in the same cognitive process. Is it possible to detect oscillatory synchrony in humans, and is it relevant to behavior? There is now converging evidence for the existence of a transient oscillatory activity in the gamma range (30-60 Hz), obtained in response to static visual objects, and having only a loose temporal relationship to stimulus onset. This so-called "induced" gamma response is much larger in response to coherent static or moving objects. However, functional variations of gamma and/or beta (15-20 Hz) oscillations are not restricted to perceptive, bottom-up mechanisms, but are also observed during visual imagery or short-term memory maintenance. Oscillations at the scalp level thus seem to reflect large-scale neural cooperativity in a variety of task-dependent networks. Human intra-cranial recordings in a short-term memory paradigm further reveal the existence and the task-dependency of oscillatory synchrony in the beta range, between focal sites separated by several centimeters and with a few milliseconds time-lag. These findings thus confirm experimentally the hypothesis of a functional role of synchronized oscillatory activity in the coordination of distributed neural activity in humans, and support Hebb's concept of short-term memory maintenance by reentrant activity within the activated network. In addition, the intra-cranial data obtained in humans and monkeys also help to better understand the neural mechanisms generating scalp-recorded oscillations.     

Functional dissociation of ongoing oscillatory brain states

The state of a neural assembly preceding an incoming stimulus is assumed to modulate the processing of subsequently presented stimuli. The nature of this state can differ with respect to the frequency of ongoing oscillatory activity. Oscillatory brain activity of specific frequency range such as alpha (8-12 Hz) and gamma (above 30 Hz) band oscillations are hypothesized to play a functional role in cognitive processing. Therefore, a selective modulation of this prestimulus activity could clarify the functional role of these prestimulus fluctuations. For this purpose, we adopted a novel non-invasive brain-computer-interface (BCI) strategy to selectively increase alpha or gamma band activity in the occipital cortex combined with an adaptive presentation of visual stimuli within specific brain states. During training, oscillatory brain activity was estimated online and fed back to the participants to enable a deliberate modulation of alpha or gamma band oscillations. Results revealed that volunteers selectively increased alpha and gamma frequency oscillations with a high level of specificity regarding frequency range and localization. At testing, alpha or gamma band activity was classified online and at defined levels of activity, visual objects embedded in noise were presented instantly and had to be detected by the volunteer. In experiment I, the effect of two levels of prestimulus gamma band activity on visual processing was examined. During phases of increased gamma band activity significantly more visual objects were detected. In experiment II, the effect was compared against increased levels of alpha band activity. An improvement of visual processing was only observed for enhanced gamma band activity. Both experiments demonstrate the specific functional role of prestimulus gamma band oscillations for perceptual processing. We propose that the BCI method permits the selective modulation of oscillatory activity and the direct assessment of behavioral consequences to test for functional dissociations of different oscillatory brain states.     

Driving oscillatory activity in the human cortex enhances motor performance

Voluntary movement is accompanied by changes in the degree to which neurons in the brain synchronize their activity within discrete frequency ranges. Two patterns of movement-related oscillatory activity stand out in human cortical motor areas. Activity in the beta frequency (15-30 Hz) band is prominent during tonic contractions but is attenuated prior to and during voluntary movement. Without such attenuation, movement may be slowed, leading to the suggestion that beta activity promotes postural and tonic contraction, possibly at a cost to the generation of new movements. In contrast, activity in the gamma (60-90 Hz) band increases during movement. The direction of change suggests that gamma activity might facilitate motor processing. In correspondence with this, increased frontal gamma activity is related with reduced reaction times. Yet the possibility remains that these functional correlations reflect an epiphenomenal rather than causal relationship. Here we provide strong evidence that oscillatory activities at the cortical level are mechanistically involved in determining motor behavior and can even improve performance. By driving cortical oscillations using noninvasive electrical stimulation, we show opposing effects at beta and gamma frequencies and interactions with motor task that reveal the potential quantitative importance of oscillations in motor behavior.     

Reshaping of bulbar odor response by nasal flow rate in the rat

Background

The impact of respiratory dynamics on odor response has been poorly studied at the olfactory bulb level. However, it has been shown that sniffing in the behaving rodent is highly dynamic and varies both in frequency and flow rate. Bulbar odor response could vary with these sniffing parameter variations. Consequently, it is necessary to understand how nasal airflow can modify and shape odor response at the olfactory bulb level.

Methodology and Principal Findings

To assess this question, we used a double cannulation and simulated nasal airflow protocol on anesthetized rats to uncouple nasal airflow from animal respiration. Both mitral/tufted cell extracellular unit activity and local field potentials (LFPs) were recorded. We found that airflow changes in the normal range were sufficient to substantially reorganize the response of the olfactory bulb. In particular, cellular odor-evoked activities, LFP oscillations and spike phase-locking to LFPs were strongly modified by nasal flow rate.

Conclusion

Our results indicate the importance of reconsidering the notion of odor coding as odor response at the bulbar level is ceaselessly modified by respiratory dynamics.     

Negative relationship between odor-induced spike activity and spontaneous oscillations in the primary olfactory system of the terrestrial slug Limax marginatus

Although primary olfactory systems in various animals display spontaneous oscillatory activity, its functional significance in olfactory processing has not been elucidated. The tentacular ganglion, the primary olfactory system of the terrestrial slug Limax marginatus, also displays spontaneous oscillatory activity at 1-2 Hz. In the present study, we examined the relationship between odor-evoked spike activity and spontaneous field potential oscillations in the tentacular nerve, representing the pathway from the primary olfactory system to the olfactory center. Neural activity was recorded from the tentacular nerve before, during and after application of various odors (garlic, carrot, and rat chow) to the sensory epithelium and the changes in firing rate and spontaneous oscillations were analyzed. We detected the baseline amplitude of the oscillations and baseline spike activity before stimulation. Odor stimulations for 20 s or 60 s evoked a transient increase in the firing rate followed by a decrease in the amplitude of spontaneous oscillations. The decrease in the amplitude was larger in the first 8 s of stimulation and subsequently showed recovery during stimulation. The amplitude of the recovered oscillations often fluctuated. Odor-evoked spikes appeared when the amplitude of the recovered oscillations was transiently small. These results suggest that the large oscillations could inhibit spike activity whereas the first transient increase in spike activity was followed by the decrease in the oscillation amplitude. Our results indicate that there is a significant negative correlation between spontaneous oscillations and odor-evoked spike activity, suggesting that the spontaneous oscillations contribute to the olfactory processing in slugs.     

Subthalamic local field beta oscillations during ongoing deep brain stimulation in Parkinson's disease in hyperacute and chronic phases

In the past years, local field potential (LFP) signals recorded from the subthalamic nucleus (STN) in patients undergoing deep brain stimulation (DBS) for Parkinson's disease (PD) disclosed that DBS has a controversial effect on STN beta oscillations recorded 2-7 days after surgery for macroelectrode implantation. Nothing is known about these DBS-induced oscillatory changes 30 days after surgery. We recorded STN LFPs during ongoing DBS in 7 patients with PD, immediately (hyperacute phase) and 30 days (chronic phase) after surgery. STN LFP recordings showed stationary intranuclear STN beta LFP activity in hyperacute and chronic phases, confirming that beta peaks were also present in chronic recordings. Power spectra of nuclei with significant beta activity (54% of the sample) showed that it decreased significantly during DBS (p=0.021) under both recording conditions. The time course of beta activity showed more evident DBS-induced changes in the chronic than in the hyperacute phase (p=0.014). DBS-induced changes in STN beta LFPs in patients undergoing DBS in chronic phase provide useful information for developing a new neurosignal-controlled adaptive DBS system.     

A new look at gamma? High- (>60 Hz) γ-band activity in cortical networks: function, mechanisms and impairment

γ-band oscillations are thought to play a crucial role in information processing in cortical networks. In addition to oscillatory activity between 30 and 60 Hz, current evidence from electro- and magnetoencephalography (EEG/MEG) and local-field potentials (LFPs) has consistently shown oscillations >60 Hz (high γ-band) whose function and generating mechanisms are unclear. In the present paper, we summarize data that highlights the importance of high γ-band activity for cortical computations through establishing correlations between the modulation of oscillations in the 60-200 Hz frequency and specific cognitive functions. Moreover, we will suggest that high γ-band activity is impaired in neuropsychiatric disorders, such as schizophrenia and epilepsy. In the final part of the paper, we will review physiological mechanisms underlying the generation of high γ-band oscillations and discuss the functional implications of low vs. high γ-band activity patterns in cortical networks.     

Synchronization of olfactory bulb mitral cells by precisely timed inhibitory inputs

Synchronized oscillatory activity at the gamma frequency (30-70 Hz) is thought to be important for information processing in many sensory systems. Here, I used patch-clamp recordings in neuron pairs in rat olfactory bulb slices to assess the mechanisms underlying such "gamma" activity in the olfactory system. Patterned electrical stimulation of afferents that mimicked a natural odor stimulus elicited rapidly synchronized spikes (lag < or = 5 ms) in mitral cells, along with oscillatory activity at the gamma (approximately 50 Hz) frequency. Analysis of coupling potentials, combined with dendritic sectioning, indicated that mitral cell synchrony was mainly driven by inhibitory postsynaptic potentials (IPSPs) imposed by GABAergic granule cells. Recordings in granule cell pairs indicated that granule cells were themselves synchronized by their excitatory inputs from mitral cells, providing a means to coordinate GABA release. These results demonstrate that rapid synchrony can emerge in a network through the precise back-and-forth interplay between neuronal populations.     

Faster, deeper, better: the impact of sniffing modulation on bulbar olfactory processing

A key feature of mammalian olfactory perception is that sensory input is intimately related to respiration. Different authors have considered respiratory dynamics not only as a simple vector for odor molecules but also as an integral part of olfactory perception. Thus, rats adapt their sniffing strategy, both in frequency and flow rate, when performing odor-related tasks. The question of how frequency and flow rate jointly impact the spatio-temporal representation of odor in the olfactory bulb (OB) has not yet been answered. In the present paper, we addressed this question using a simulated nasal airflow protocol on anesthetized rats combined with voltage-sensitive dye imaging (VSDi) of odor-evoked OB glomerular maps. Glomerular responses displayed a tonic component during odor stimulation with a superimposed phasic component phase-locked to the sampling pattern. We showed that a high sniffing frequency (10 Hz) retained the ability to shape OB activity and that the tonic and phasic components of the VSDi responses were dependent on flow rate and inspiration volume, respectively. Both sniffing parameters jointly affected OB responses to odor such that the reduced activity level induced by a frequency increase was compensated by an increased flow rate.     

Smell-induced gamma oscillations in human olfactory cortex are required for accurate perception of odor identity

Studies of neuronal oscillations have contributed substantial insight into the mechanisms of visual, auditory, and somatosensory perception. However, progress in such research in the human olfactory system has lagged behind. As a result, the electrophysiological properties of the human olfactory system are poorly understood, and, in particular, whether stimulus-driven high-frequency oscillations play a role in odor processing is unknown. Here, we used direct intracranial recordings from human piriform cortex during an odor identification task to show that 3 key oscillatory rhythms are an integral part of the human olfactory cortical response to smell: Odor induces theta, beta, and gamma rhythms in human piriform cortex. We further show that these rhythms have distinct relationships with perceptual behavior. Odor-elicited gamma oscillations occur only during trials in which the odor is accurately perceived, and features of gamma oscillations predict odor identification accuracy, suggesting that they are critical for odor identity perception in humans. We also found that the amplitude of high-frequency oscillations is organized by the phase of low-frequency signals shortly following sniff onset, only when odor is present. Our findings reinforce previous work on theta oscillations, suggest that gamma oscillations in human piriform cortex are important for perception of odor identity, and constitute a robust identification of the characteristic electrophysiological response to smell in the human brain. Future work will determine whether the distinct oscillations we identified reflect distinct perceptual features of odor stimuli.

Intracranial recordings from human olfactory cortex reveal a characteristic spectrotemporal response to odors, including theta, beta and gamma oscillations, and show that high-frequency responses are critical for accurate perception of odors.     

Dynamic representation of odours by oscillating neural assemblies

Stimulus evoked oscillatory synchronization of neural assemblies has been most clearly documented in the olfactory and visual systems. Recent results with the olfactory system of locusts show that information about odour identity is contained in spatial and temporal aspects of an oscillatory population response. This suggests that brain oscillations may reflect a common reference for messages encoded in time. Although stimulus-evoked oscillatory phenomena are reliable, their roles in perception, memory and pattern recognition remain to be demonstrated. Using honey bees, we demonstrated that odour encoding involves, as in locusts, the oscillatory synchronization of assemblies of neurons, and that this synchronization is, here also, selectively abolished by the GABA receptor antagonist picrotoxin. In collaboration with Dr Brian Smith's laboratory, we showed, using a behavioural learning paradigm, that picrotoxin-induced desynchronization impairs the discrimination of molecularly similar odourants, but not that of dissimilar odours. It appears, therefore, that oscillatory synchronization of neuronal assemblies is relevant, and essential for fine odour discrimination. Finally, experiments with locust mushroom body neurons, two synapses downstream from the antennal lobe, indicate that their responses to odours become less specific when antennal lobe neurons are desynchronized by picrotoxin injection. These results suggest that oscillatory synchronization and the kind of temporal encoding it affords provide an additional dimension by which the brain can segment spatially overlapping stimulus representations.     

Human gamma oscillations during slow wave sleep

Neocortical local field potentials have shown that gamma oscillations occur spontaneously during slow-wave sleep (SWS). At the macroscopic EEG level in the human brain, no evidences were reported so far. In this study, by using simultaneous scalp and intracranial EEG recordings in 20 epileptic subjects, we examined gamma oscillations in cerebral cortex during SWS. We report that gamma oscillations in low (30-50 Hz) and high (60-120 Hz) frequency bands recurrently emerged in all investigated regions and their amplitudes coincided with specific phases of the cortical slow wave. In most of the cases, multiple oscillatory bursts in different frequency bands from 30 to 120 Hz were correlated with positive peaks of scalp slow waves ("IN-phase" pattern), confirming previous animal findings. In addition, we report another gamma pattern that appears preferentially during the negative phase of the slow wave ("ANTI-phase" pattern). This new pattern presented dominant peaks in the high gamma range and was preferentially expressed in the temporal cortex. Finally, we found that the spatial coherence between cortical sites exhibiting gamma activities was local and fell off quickly when computed between distant sites. Overall, these results provide the first human evidences that gamma oscillations can be observed in macroscopic EEG recordings during sleep. They support the concept that these high-frequency activities might be associated with phasic increases of neural activity during slow oscillations. Such patterned activity in the sleeping brain could play a role in off-line processing of cortical networks.     

Role of frequency mismatch in neuronal communication through coherence

Neuronal gamma oscillations have been described in local field potentials of different brain regions of multiple species. Gamma oscillations are thought to reflect rhythmic synaptic activity organized by inhibitory interneurons. While several aspects of gamma rhythmogenesis are relatively well understood, we have much less solid evidence about how gamma oscillations contribute to information processing in neuronal circuits. One popular hypothesis states that a flexible routing of information between distant populations occurs via the control of the phase or coherence between their respective oscillations. Here, we investigate how a mismatch between the frequencies of gamma oscillations from two populations affects their interaction. In particular, we explore a biophysical model of the reciprocal interaction between two cortical areas displaying gamma oscillations at different frequencies, and quantify their phase coherence and communication efficiency. We observed that a moderate excitatory coupling between the two areas leads to a decrease in their frequency detuning, up to ～6 Hz, with no frequency locking arising between the gamma peaks. Importantly, for similar gamma peak frequencies a zero phase difference emerges for both LFP and MUA despite small axonal delays. For increasing frequency detunings we found a significant decrease in the phase coherence (at non-zero phase lag) between the MUAs but not the LFPs of the two areas. Such difference between LFPs and MUAs behavior is due to the misalignment between the arrival of afferent synaptic currents and the local excitability windows. To test the efficiency of communication we evaluated the success of transferring rate-modulations between the two areas. Our results indicate that once two populations lock their peak frequencies, an optimal phase relation for communication appears. However, the sensitivity of locking to frequency mismatch suggests that only a precise and active control of gamma frequency could enable the selection of communication channels and their directionality.     

Selective and reversible blockage of a fatty acid odour response in the olfactory bulb of the frog (Rana temporaria).

The lectin concanavalin A (ConA) when applied to the olfactory mucosa (OM) of frog and rat, is reported to partially inhibit electro-olfactogram (EOG) responses to fatty acid odours. Control odours like isoamyl acetate were not affected. We have now studied in the frog whether this treatment affects the corresponding olfactory bulb (OB) response. The OB surface was impregnated with a voltage-sensitive dye (RH 414). Spatial and temporal patterns of odour response were measured by changes in dye fluorescence that occur when OB neurons fire. The apparatus, consisted of an epi-fluorescent microscope coupled to a 64 x 64 pixel CCD photodetection camera. This allowed imaging over an 0.9 mm2 area of the OB glomerular layer to high resolution. When the frog OM was bathed with 5 mg ml(-1) ConA in Ringer's solution, the n-butyric acid odour response in the OB largely disappeared while the isoamyl acetate response did not change. When this experiment was repeated in the presence of 20 mM methyl alpha-D mannopyranoside (a ConA inhibitor), ConA failed to inhibit the n-butyric acid response. Moreover the ConA effect was partially reversible. A Ringer's wash of the OM after ConA treatment, partially restored the OB response to n-butyric acid. Thus the olfactory bulb results seem compatible with the EOG results and reinforce the notion that ConA selectively prevents n-butyric acid sensitive olfactory receptor neurons from firing. Chemical modification of the OM and their effect on OB response patterns may provide a useful approach to investigate olfactory quality coding.     

Characterization of electro-olfactogram oscillations and their computational reconstruction

Electro-olfactogram (EOG) oscillations induced by odorant stimulation have been often reported in various vertebrates from fishes to mammals. However, the mechanism of generation of EOG oscillations remains unclear. In the present study, we first characterized the properties of EOG oscillations induced by amino acid odorants in the rainbow trout and then performed a computer simulation based on the main assumption that olfactory receptor neurons (ORNs) have intrinsic oscillatory properties due to two types of voltage-gated ion channels, which have not yet been reported in vertebrate ORNs. EOG oscillations appeared mostly on the peak and decay phases of negative EOG responses, when odorant stimuli at high intensity flowed regularly anterior to posterior olfactory lamellae in the olfactory organ. The appearance of EOG oscillations was dependent on the odorant intensity but not on the flow rate. The maximum amplitude and the maximum power frequency of EOG oscillations were 3.51 +/- 3.35 mV (mean +/- SD, n = 232, range 0.12-16.79 mV) and 10.59 +/- 5.05 Hz (mean +/- SD, n = 232, range 3.51-40.03 Hz), respectively. The simulation represented sufficiently well the characteristics of EOG oscillations; occurrence at high odorant concentration, odorant concentration-dependent amplitude and the maximum power frequency range actually observed. Our results suggest that EOG oscillations are due to the intrinsic oscillatory properties of individual ORNs, which have two novel types of voltage-gated ion channels (resonant and amplifying channels). The simulation program for Macintosh ('oscillation 3.2.4' for MacOS 8.6 or later) is available on the world wide web (http://bio2.sci.hokudai.ac.jp/bio/chinou1/noriyo_home.html).     

Dynamic Changes in Single Unit Activity and Gamma Oscillations in a Thalamocortical Circuit during Rapid Instrumental Learning

The medial prefrontal cortex (mPFC) and mediodorsal thalamus (MD) together form a thalamocortical circuit that has been implicated in the learning and production of goal-directed actions. In this study we measured neural activity in both regions simultaneously, as rats learned to press a lever to earn food rewards. In both MD and mPFC, instrumental learning was accompanied by dramatic changes in the firing patterns of the neurons, in particular the rapid emergence of single-unit neural activity reflecting the completion of the action and reward delivery. In addition, we observed distinct patterns of changes in the oscillatory LFP response in MD and mPFC. With learning, there was a significant increase in theta band oscillations (6–10 Hz) in the MD, but not in the mPFC. By contrast, gamma band oscillations (40–55 Hz) increased in the mPFC, but not in the MD. Coherence between these two regions also changed with learning: gamma coherence in relation to reward delivery increased, whereas theta coherence did not. Together these results suggest that, as rats learned the instrumental contingency between action and outcome, the emergence of task related neural activity is accompanied by enhanced functional interaction between MD and mPFC in response to the reward feedback.