scholarly journals Cannabis Vapour Exposure Alters Neural Circuit Oscillatory Activity In A Neurodevelopmental Model Of Schizophrenia: Exploring The Differential Impact Of Cannabis Constituents

2021 ◽  
Author(s):  
Bryan W. Jenkins ◽  
Shoshana Buckhalter ◽  
Melissa L. Perreault ◽  
Jibran Y. Khokhar

AbstractCannabis use is highly prevalent in patients with schizophrenia and worsens the course of the disorder. To understand the causal impacts of cannabis on schizophrenia-related oscillatory disruptions, we herein investigated the impact of exposure to cannabis vapour (containing delta-9-tetrahydrocannabinol [THC] or balanced THC and cannabidiol [CBD]) on oscillatory activity in the neonatal ventral hippocampal lesion (NVHL) rat model of schizophrenia. Male Sprague Dawley rats underwent NVHL or sham surgeries on postnatal day 7. In adulthood, electrodes were implanted targeting the cingulate cortex (Cg), the prefrontal cortex (PFC), the dorsal hippocampus (HIP), and the nucleus accumbens (NAc). Local field potential recordings were obtained following exposure to two strains of vapourized cannabis flower (with ~10% THC or ~10% balanced THC:CBD) in a cross-over design with a two-week wash-out period between exposures. Compared to controls, NVHL rats had reduced baseline gamma power in the Cg, dHIP, and NAc, and reduced high-gamma coherence between the dHIP-Cg. THC-only vapour broadly suppressed oscillatory power and coherence, even beyond the baseline suppressions observed in NHVL rats. Balanced THC:CBD vapour appeared to ameliorate the THC-induced impacts on power and coherence in both sham and NVHL rats. For NVHL rats, THC-only vapour also normalized the baseline dHIP-Cg high-gamma coherence deficits. NHVL rats also demonstrated a 20ms delay in dHIP theta to high-gamma phase coupling, which was ameliorated by both exposures in the PFC and NAc. In conclusion, THC-only cannabis vapour suppressed oscillatory activity in NVHL and sham rats, while balanced THC:CBD vapour may ameliorate some of these effects.

Author(s):  
Peter Gombkoto ◽  
Matthew Gielow ◽  
Peter Varsanyi ◽  
Candice Chavez ◽  
Laszlo Zaborszky

AbstractBasal forebrain (BF) cholinergic neurons provide the cerebral cortex with acetylcholine. Despite the long-established involvement of these cells in sensory processing, attention, and memory, the mechanisms by which cholinergic signaling regulates cognitive processes remain elusive. In this study, we recorded spiking and local field potential data simultaneously from several locations in the BF, and sites in the orbitofrontal and visual cortex in transgenic ChAT-Cre rats performing a visual discrimination task. We observed distinct differences in the fine spatial distributions of gamma coherence values between specific basalo-cortical and cortico-cortical sites that shifted across task phases. Additionally, cholinergic firing induced spatial changes in cortical gamma power, and optogenetic activation of BF increased coherence between specific cortico-cortical sites, suggesting that the cholinergic system contributes to selective modulation of cortico-cortical circuits. Furthermore, the results suggest that cells in specific BF locations are dynamically recruited across behavioral epochs to coordinate interregional cortical processes underlying cognition.


2019 ◽  
Author(s):  
Agrita Dubey ◽  
Supratim Ray

AbstractElectrocorticogram (ECoG), obtained from macroelectrodes placed on the cortex, is typically used in drug-resistant epilepsy patients, and is increasingly being used to study cognition in humans. These studies often use power in gamma (30-70 Hz) or high-gamma (>80 Hz) ranges to make inferences about neural processing. However, while the stimulus tuning properties of gamma/high-gamma power have been well characterized in local field potential (LFP; obtained from microelectrodes), analogous characterization has not been done for ECoG. Using a hybrid array containing both micro and ECoG electrodes implanted in the primary visual cortex of two female macaques, we compared the stimulus tuning preferences of gamma/high-gamma power in LFP versus ECoG and found them to be surprisingly similar. High-gamma power, thought to index the average firing rate around the electrode, was highest for the smallest stimulus (0.3° radius), and decreased with increasing size in both LFP and ECoG, suggesting local origins of both signals. Further, gamma oscillations were similarly tuned in LFP and ECoG to stimulus orientation, contrast and spatial frequency. This tuning was significantly weaker in electroencephalogram (EEG), suggesting that ECoG is more like LFP than EEG. Overall, our results validate the use of ECoG in clinical and basic cognitive research.


2019 ◽  
Author(s):  
Matt Gaidica ◽  
Amy Hurst ◽  
Christopher Cyr ◽  
Daniel K. Leventhal

AbstractThe thalamus plays a central role in generating circuit-level neural oscillations believed to coordinate brain activity over large spatiotemporal scales. Such thalamic influences are well-documented for sleep rhythms and in sensory systems, but the relationship between thalamic activity, motor circuit local field potential (LFP) oscillations, and behavior is unknown. We recorded wideband motor thalamic (Mthal) electrophysiology as healthy rats performed a two-alternative forced choice task. The power of delta (1−4 Hz), beta (13−30 Hz), low gamma (30−70 Hz), and high gamma (70−200 Hz) oscillations were strongly modulated by task performance. As in cortex, delta phase predicted beta/low gamma power and reaction time. Furthermore, delta phase differentially predicted spike timing in functionally distinct populations of Mthal neurons, which also predicted task performance and beta power. These complex relationships suggest mechanisms for commonly observed LFP-LFP and spike-LFP interactions, as well as subcortical influences on motor output.


2018 ◽  
Author(s):  
A Chrabaszcz ◽  
WJ Neumann ◽  
O Stretcu ◽  
WJ Lipski ◽  
A Bush ◽  
...  

ABSTRACTThe sensorimotor cortex is somatotopically organized to represent the vocal tract articulators, such as lips, tongue, larynx, and jaw. How speech and articulatory features are encoded at the subcortical level, however, remains largely unknown. We analyzed local field potential (LFP) recordings from the subthalamic nucleus (STN) and simultaneous electrocorticography recordings from the sensorimotor cortex of 11 patients (1 female) with Parkinson’s disease during implantation of deep brain stimulation (DBS) electrodes, while patients read aloud three-phoneme words. The initial phonemes involved either articulation primarily with the tongue (coronal consonants) or the lips (labial consonants). We observed significant increases in high gamma (60–150 Hz) power in both the STN and the sensorimotor cortex that began before speech onset and persisted for the duration of speech articulation. As expected from previous reports, in the sensorimotor cortex, the primary articulator involved in the production of the initial consonant was topographically represented by high gamma activity. We found that STN high gamma activity also demonstrated specificity for the primary articulator, although no clear topography was observed. In general, subthalamic high gamma activity varied along the ventral-dorsal trajectory of the electrodes, with greater high gamma power recorded in the more dorsal locations of the STN. These results demonstrate that articulator-specific speech information is contained within high gamma activity of the STN, with similar temporal but less specific topographical organization, compared to similar information encoded in the sensorimotor cortex.SIGNIFICANCE STATEMENTClinical and electrophysiological evidence suggests that the subthalamic nucleus is involved in speech, however, this important basal ganglia node is ignored in current models of speech production. We previously showed that subthalamic nucleus neurons differentially encode early and late aspects of speech production, but no previous studies have examined subthalamic functional organization for speech articulators. Using simultaneous local field potential recordings from the sensorimotor cortex and the subthalamic nucleus in patients with Parkinson’s disease undergoing deep brain stimulation surgery, we discovered that subthalamic nucleus high gamma activity tracks speech production at the level of vocal tract articulators, with high gamma power beginning to increase prior to the onset of vocalization, similar to cortical articulatory encoding.


2020 ◽  
Vol 14 ◽  
Author(s):  
John D. Griffiths ◽  
Anthony Randal McIntosh ◽  
Jeremie Lefebvre

Rhythmic activity in the brain fluctuates with behaviour and cognitive state, through a combination of coexisting and interacting frequencies. At large spatial scales such as those studied in human M/EEG, measured oscillatory dynamics are believed to arise primarily from a combination of cortical (intracolumnar) and corticothalamic rhythmogenic mechanisms. Whilst considerable progress has been made in characterizing these two types of neural circuit separately, relatively little work has been done that attempts to unify them into a single consistent picture. This is the aim of the present paper. We present and examine a whole-brain, connectome-based neural mass model with detailed long-range cortico-cortical connectivity and strong, recurrent corticothalamic circuitry. This system reproduces a variety of known features of human M/EEG recordings, including spectral peaks at canonical frequencies, and functional connectivity structure that is shaped by the underlying anatomical connectivity. Importantly, our model is able to capture state- (e.g., idling/active) dependent fluctuations in oscillatory activity and the coexistence of multiple oscillatory phenomena, as well as frequency-specific modulation of functional connectivity. We find that increasing the level of sensory drive to the thalamus triggers a suppression of the dominant low frequency rhythms generated by corticothalamic loops, and subsequent disinhibition of higher frequency endogenous rhythmic behaviour of intracolumnar microcircuits. These combine to yield simultaneous decreases in lower frequency and increases in higher frequency components of the M/EEG power spectrum during states of high sensory or cognitive drive. Building on this, we also explored the effect of pulsatile brain stimulation on ongoing oscillatory activity, and evaluated the impact of coexistent frequencies and state-dependent fluctuations on the response of cortical networks. Our results provide new insight into the role played by cortical and corticothalamic circuits in shaping intrinsic brain rhythms, and suggest new directions for brain stimulation therapies aimed at state-and frequency-specific control of oscillatory brain activity.


2008 ◽  
Vol 100 (1) ◽  
pp. 422-430 ◽  
Author(s):  
Romulo A. Fuentes ◽  
Marcelo I. Aguilar ◽  
María L. Aylwin ◽  
Pedro E. Maldonado

Odorants induce specific modulation of mitral/tufted (MT) cells' firing rate in the mammalian olfactory bulb (OB), inducing temporal patterns of neuronal discharge embedded in an oscillatory local field potential (LFP). While most studies have examined anesthetized animals, little is known about the firing rate and temporal patterns of OB single units and population activity in awake behaving mammals. We examined the firing rate and oscillatory activity of MT cells and LFP signals in behaving rats during two olfactory tasks: passive exposure (PE) and two-alternative (TA) choice discrimination. MT inhibitory responses are predominant in the TA task (76.5%), whereas MT excitatory responses predominate in the PE task (59.2%). Rhythmic discharge in the 12- to 100-Hz range was found in 79.0 and 68.9% of MT cells during PE and TA tasks, respectively. Most odorants presented in PE task increase rhythmic discharges at frequencies >50 Hz, whereas in TA, one of four odorants produced a modest increment <40 Hz. LFP oscillations were clearly modulated by odorants during the TA task, increasing their oscillatory power at frequencies centered at 20 Hz and decreasing power at frequencies >50 Hz. Our results indicate that firing rate responses of MT cells in awake animals are behaviorally modulated with inhibition being a prominent feature of this modulation. The occurrence of oscillatory patterns in single- and multiunitary discharge is also related to stimulation and behavioral context, while the oscillatory patterns of the neuronal population showed a strong dependence on odorant stimulation.


2021 ◽  
Author(s):  
Jason Samaha ◽  
Michael X Cohen

Oscillatory neural dynamics are highly non-stationary and require methods capable of quantifying time-resolved changes in rhythmic activity in order to understand neural function. Recently, a method termed 'frequency sliding' was introduced to estimate the instantaneous frequency of oscillatory activity, providing a means of tracking temporal changes in the dominant frequency within a sub-band of field potential recordings. Here, the ability of frequency sliding to recover ground-truth oscillatory frequency in simulated data is tested while the exponent (slope) of the 1/fx component of the signal power spectrum is systematically varied, mimicking real electrophysiological data. The results show that 1) in the presence of 1/f activity, frequency sliding systematically underestimates the true frequency of the signal, 2) the magnitude of underestimation is correlated with the steepness of the slope, suggesting that, if unaccounted for, slope changes could be misinterpreted as frequency changes, 3) the impact of slope on frequency estimates interacts with oscillation amplitude, indicating that changes in oscillation amplitude alone may also influence instantaneous frequency estimates in the presence of strong 1/f activity; and 4) analysis parameters such as filter bandwidth and location also mediate the influence of slope on estimated frequency, indicating that these settings should be considered when interpreting estimates obtained via frequency sliding. The origin of these biases resides in the output of the filtering step of frequency sliding, whose energy is biased towards lower frequencies precisely because of the 1/f structure of the data. We discuss several strategies to mitigate these biases and provide a proof-of-principle for a 1/f normalization strategy.


2021 ◽  
pp. 1-8
Author(s):  
S. Melker Hagsäter ◽  
Robert Pettersson ◽  
Axel Holmäng ◽  
Elias Eriksson

Abstract Objective: Whereas numerous experimental and clinical studies suggest a complex involvement of serotonin in the regulation of anxiety, it remains to be clarified if the dominating impact of this transmitter is best described as anxiety-reducing or anxiety-promoting. The aim of this study was to assess the impact of serotonin depletion on acquisition, consolidation, and expression of conditioned fear. Methods: Male Sprague–Dawley rats were exposed to foot shocks as unconditioned stimulus and assessed with respect to freezing behaviour when re-subjected to context. Serotonin depletion was achieved by administration of a serotonin synthesis inhibitor, para-chlorophenylalanine (PCPA) (300 mg/kg daily × 3), (i) throughout the period from (and including) acquisition to (and including) expression, (ii) during acquisition but not expression, (iii) after acquisition only, and (iv) during expression only. Results: The time spent freezing was significantly reduced in animals that were serotonin-depleted during the entire period from (and including) acquisition to (and including) expression, as well as in those being serotonin-depleted during either acquisition only or expression only. In contrast, PCPA administrated immediately after acquisition, that is during memory consolidation, did not impact the expression of conditioned fear. Conclusion: Intact serotonergic neurotransmission is important for both acquisition and expression of context-conditioned fear.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bin Wang ◽  
Chuanliang Han ◽  
Tian Wang ◽  
Weifeng Dai ◽  
Yang Li ◽  
...  

AbstractStimulus-dependence of gamma oscillations (GAMMA, 30–90 Hz) has not been fully understood, but it is important for revealing neural mechanisms and functions of GAMMA. Here, we recorded spiking activity (MUA) and the local field potential (LFP), driven by a variety of plaids (generated by two superimposed gratings orthogonal to each other and with different contrast combinations), in the primary visual cortex of anesthetized cats. We found two distinct narrow-band GAMMAs in the LFPs and a variety of response patterns to plaids. Similar to MUA, most response patterns showed that the second grating suppressed GAMMAs driven by the first one. However, there is only a weak site-by-site correlation between cross-orientation interactions in GAMMAs and those in MUAs. We developed a normalization model that could unify the response patterns of both GAMMAs and MUAs. Interestingly, compared with MUAs, the GAMMAs demonstrated a wider range of model parameters and more diverse response patterns to plaids. Further analysis revealed that normalization parameters for high GAMMA, but not those for low GAMMA, were significantly correlated with the discrepancy of spatial frequency between stimulus and sites’ preferences. Consistent with these findings, normalization parameters and diversity of high GAMMA exhibited a clear transition trend and region difference between area 17 to 18. Our results show that GAMMAs are also regulated in the form of normalization, but that the neural mechanisms for these normalizations might differ from those of spiking activity. Normalizations in different brain signals could be due to interactions of excitation and inhibitions at multiple stages in the visual system.


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