Canada

Perineuronal nets (PNNs) are extracellular matrices that preferentially surround parvalbumin-positive (PV+) interneurons. Since PV+ neurons shape neural dynamics and plasticity, PNNs surrounding PV+ neurons have been proposed to regulate neural function. Much of the research on PNNs has centered on their role in sensory circuits, and little is known about how PNNs in sensorimotor structures affect behavioral expression. Here, we analyze the relationship between PNN and PV expression in sensorimotor systems and vocal performance in songbirds. Because songbirds, like humans, learn their vocalizations and use auditory feedback for vocal learning and control, songbirds are powerful animal models to reveal neural mechanisms of sensorimotor plasticity and function. We specifically relate PNN expression around PV+ neurons in forebrain and basal ganglia circuitry to the performance of learned vocalizations in the zebra finch. We hypothesize that, just as PNNs in sensory processing areas consolidate the sensory representations, PNNs in sensorimotor structures could consolidate sensorimotor commands for vocalizations. In this respect, we propose that more PV+ neurons are surrounded by PNNs in birds that produce more stereotyped vocalizations. Given that developmental exposure to song and age affect song stereotypy, we investigate this relationship in juvenile and adult birds that are either reared normally or deprived of song exposure throughout development. Our studies hope to provide further insight into the influence of PNNs on behavioral control and plasticity.

CAN-ACN 2021

Investigating the influence of perineuronal nets surrounding parvalbumin-positive neurons in sensorimotor circuitry on motor performance

sensorimotor system

vocal performance

parvalbumin

perineuronal nets

Colleagues and Friends:

I am very happy to welcome you to the 14th annual Canadian Neuroscience Meeting, and to the first virtual edition of our meeting. I want to highlight the important work the CAN meeting chair, **Roger Thompson** and co-chair, **Alyson Fournier**, did to put together the great program we are offering this year. Moving to a virtual format required a complete re-design of the program, and both Roger and Alyson did a splendid job in providing us with an appealing and well adapted program for our first virtual event. I wish to thank them for this very important effort.

Highlights of this year’s scientific meeting include invited speakers **Michael Hausser, Franck Polleux, Gwyneth Card, Magdalena Götz**and Brain Prize winner **Huda Zoghbi**. Plenary and parallel symposia, proposed by our members complete our diverse [scientific program.](https://can-acn.org/meeting-2021/program-2021/)

The 2021 Advocacy session, chaired and organized by CAN advocacy committee chair **Karun Singh**, will feature a special lecture and question period with Member of Parliament and past Science Minister **Kirsty Duncan**. This will be followed by a short overview of CAN’s advocacy activities over the last year. We invite you to participate in this session for insight from Dr. Duncan on the workings of Parliament Hill, and to learn more about what CAN has been doing to promote neuroscience research in Canada.

We are also excited to host **Lisa Willis** in the Equity Diversity and Inclusion session, organized by EDI committee chair **Jibran Khokhar**.

A special highlight of our meeting will be the lectures by award-winning young neuroscientists. We are please to host the CAN 2020 Young Investigator Award winner **Mihaela Iordanova**, and CAN 2021 Young Investigator Award winners **Aaron Phillips** and **Tabrez Siddiqui**. Highlights will also include presentation by the top three winners of the CAN-CIHR-INMHA Brain Star Award winners, **Claire Gizowski, Nuria Daviu Abant** and **Lukas Tamayo-Orrego**.

Independently organized satellite symposia complement and complete this exciting program, check them out here: https://can-acn.org/meeting-2021/2021-satellite-symposia/

Some of the most engaging sessions are always the poster sessions featuring the work of our trainees, so make sure to log in to Gather Town during the poster sessions to chat with the presenters.
We hope you enjoy this program, and look forward to welcoming you, virtually.

Shernaz Bamji

President of the Canadian Association for Neuroscience

![](https://assets.underline.io/uploads/markdown_image/1/image/b9aea25343a87d5aac3b9367dc780974.jpg)



Please head to https://can-acn.org/meeting-2021/registration-2021/ to register. 

14th Canadian Neuroscience Meeting from August 23rd-25th

poster

The prevalence of many chronic pain syndromes differs across sex. Recent studies have identified differences in immune signalling within spinal nociceptive circuits as a potential mediator. Although it has been proposed that sex-specific pain mechanisms converge once they reach neurons within the superficial dorsal horn (SDH), direct investigations using rodent and human preclinical pain models have been lacking. Here, we discovered that in the Freund's Adjuvant in vivo model of inflammatory pain, where both male and female rats display tactile allodynia, a pathological coupling between loss of inhibition and NMDA receptor potentiation within SDH neurons was observed in male but not female rats. Unlike males, the neuroimmune mediator BDNF failed to downregulate inhibitory signalling elements and upregulate excitatory elements in female rats, resulting in no effect of ex vivo BDNF on synaptic NMDA receptor responses in female lamina I neurons. Importantly, this sex difference in spinal pain processing was conserved from rodents to humans. As in rodents, ex vivo spinal treatment with BDNF downregulated markers of disinhibition and upregulated markers of facilitated excitation in SDH neurons from male but not female human organ donors. Ovariectomy in female rats recapitulated the male pathological pain phenotype. The discovery of sexual dimorphism in a central neuronal mechanism of chronic pain across species provides a foundational step towards a better understanding and treatment of pain for both sexes.

Sexual dimorphism in a neuronal mechanism of spinal hyperexcitability across rodent and human models of pathological pain

Natural stimuli display complex spatiotemporal characteristics. In order to encode such stimuli efficiently, sensory systems must continuously adapt by changing their response properties. The computational role of such adaptation remains poorly understood because adaptation can increase coding ambiguity. We investigated how vestibular thalamocortical neurons (VTN) and their afferent input within the vestibular nuclei (VON) respond to simple artificial and complex natural selfmotion stimuli in rhesus macaques. We found that both groups displayed comparable response properties to artificial stimuli which led to ambiguity. While such ambiguity persisted for artificial stimuli for VON, VTN instead faithfully followed the timecourse of natural selfmotion stimuli. A model including gain adaptation successfully reproduced our experimental data. Our results challenge the common wisdom that adaptation leads to ambiguity by showing that such adaptation actually leads to unambiguous encoding of natural stimuli. Second, we investigated the role of these VTN in the perception of selfmotion. We tested whether their responses can account for violation of Weber's law, i.e. discrimination performance is enhanced at higher stimulus amplitudes. While neural gain decreased as a function of stimulus amplitude, neural variability saturated at high values. As a result, neural populations thresholds saturated and agreed with perception. Taken together, we provide novel insights as to how variability and gain control contribute to encoding of natural stimuli with continually varying statistics.

Gain adaptation and variability of vestibular corticothalamic neurons shape our perception of natural self motion stimuli

The transient sensations experienced by the vestibular system are critical for everyday activities such as gaze stabilization and the perception of self-motion. Accordingly, the investigation of vestibular neural coding would greatly benefit from the use of optogenetic methods; with which neuronal activity can be precisely and reliably modulated with high temporal precision. Due to our shared bipedality and close evolutionary origins, non-human primates (NHPs) are the ideal model animals. However, unlike application in invertebrates and rodents, optogenetic techniques using NHPs have not been well established, requiring researchers to infer the best approach. This project aims to provide robust results of NHP optogenetics in the vestibular system through in-vivo injection of an opsin adenovirus to key interconnected vestibular cortical and subcortical areas: the parietoinsular vestibular cortex (PIVC) and the vestibular nuclei in the brainstem of cynomolgus macaques. We can determine the efficacy and specificity of our vectors, chosen based on anatomical differences between the target regions, and evaluate opsin expression using histological methods such as immunohistochemistry and fluorescence microscopy. With the confirmation of histological expression, this project will open the door to confidently employing optogenetic methods to study vestibular electrophysiology and the behaviours it codes for, as well as to investigate feedback between our cortical and subcortical areas of interest.

Optogenetic expression in the cortical and subcortical areas of the non-human primate vestibular system

Previous studies have focused on the encoding of the first-order features of vestibular stimuli, but few studies, to date, have studied the encoding of the second-order attribute that consist of changes in vestibular stimuli amplitude or envelope. Because envelopes are critical for perception, we investigated if and how vestibular only neurons in the vestibular nuclei, known to mediate self-motion perception, encode the envelope attribute of the head motion stimulus. Specifically, we studied neural responses to stimuli consisting of a noisy waveform whose envelope varied sinusoidally at lower frequency. Importantly, stimulus amplitude was kept low such as not to elicit static nonlinearities from afferents (e.g., rectification, saturation). Our results show that the envelope attribute of the stimulus is encoded at single-neuron level in the vestibular nuclei. On average, we found that the gain of the neuron's response to the envelope remained constant across frequencies (p = 0.24). Moreover, the neuron's response shows a slight phase lead that increases as the frequency of the envelope increases (p=0.01). We found that static nonlinearities do not account for neural envelope response. Finally, we calculated the discrimination threshold and found higher values than that found in the Thalamus and for perception. Overall, our results will have important implication in our understanding of how early processing of vestibular signal can encode second-order attributes of head motion that will further be used to ensure stable perception of the world and accurate motor control.

Second-order attribute of head motion is encoded at single-neuron level in the vestibular nuclei

Self motion is composed of both rotational and translational motions which occur with characteristic statistics in everyday life. In the context of rotation, we have previously shown that neurons at the first central stage of vestibular processing (VN) are adapted to match their tuning curves to the statistics of natural rotation. This strategy effectively removes redundancy in the neural response, and produces responses which are independent of frequency (i.e. temporally whitened). However, unlike for rotation, translation sensitive neurons display significantly more heterogeneity in their tuning curves to artificial stimuli, and their responses to natural stimuli which cover the full physiological range of motion frequencies has not been explored. Here we investigated whether and, if so, how the responses of translation sensitive vestibular-only (otolith VO) cells in the VN of awake behaving macaques are adapted to naturalistic translation stimuli. Our results indicate that otolith VOs are not consistently matched to natural statistics in the same way as their rotation-sensitive counterparts, and instead fall roughly into 3 categories covering a range from strongly low-pass filtered to optimally whitened responses. This study is the first to examine the responses of otolith VO neurons in the context of natural self-motion, and suggests that low-pass filtered, faithful reconstruction, and optimally encoded representations of the stimulus may each be implemented in the translational vestibular system via parallel encoding strategies.

Neuronal sensitivity and variability mediate 3 parallel strategies for encoding natural translations in the primate vestibular system

Clinical data proposes that the common street drug MDMA (ecstasy) increases water intake by inducing the sensation of thirst and promoting fluid retention by the kidney. These effects account for the high incidence of hyponatremia (low blood sodium and excel water in serum) in patients visiting hospital emergency departments as a result of experiencing headaches and dizziness (and other signs of hyponatremia) following ingestion of MDMA. Clinical as well as rodent studies also reveal an increase in serum vasopressin levels when MDMA is ingested or administered, which is likely a key factor in fluid retention. To investigate the neurophysiological mechanisms underlying these effects brain slices obtained from transgenic rat brains were prepared at a specific angle to preserve circuitry important for the regulation of thirst and vasopressin release. Whole cell current and voltage clamp recordings from identified vasopressin neurons revealed that a bath application of MDMA causes an excitatory response; mediated by membrane depolarization. Moreover, a proportion of tonically active vasopressin neurons were observed to transition to a phasic firing pattern known to facilitate peptide release. These results suggest that MDMA can act directly on neurons controlling vasopressin thereby increasing the likelihood of fluid retention.

Mechanisms of MDMA induced vasopressin release in rats

Our research group has recently reported that nicotine, cocaine, and their conditioned contextual stimuli (CS), enhance object memory consolidation via noradrenergic and dopaminergic receptors. This suggests the hypothesis that the neuropharmacology of unconditioned and conditioned memory modulation is not influenced by drug class. To test the hypothesis, male Sprague-Dailey rats received infusions of the nicotinic receptor antagonist mecamylamine (MEC) within the perirhinal cortex (PRh); a cortical region well known to be involved in consolidation object memory. To establish the drug CSs, rats were confined for 2 h in a chamber (the CS+) after injections of 0.4 mg/kg nicotine or 20 mg/kg cocaine, and in another chamber (the CS−) after injections of vehicle. This was repeated over 10 d (5 drug/CS+ and 5 vehicle/CS− pairings in total). Surprisingly, it was found that the memory enhancing action of post-sample 0.4 mg/kg nicotine, but not 20 mg/kg cocaine, was blocked by intra-PRh infusions of 10 and 30 μg/side MEC. Moreover, the memory enhancing effects of the nicotine CS, but not cocaine CS, were also blocked by 30 μg/side MEC. Overall, these data indicate that a nicotine CS promotes memory consolidation by enhancing PRh cholinergic activity similar to the central effects of nicotine itself, but this is not the case for cocaine and cocaine CSs. These results suggest that in addition to mimicking the behavioural effects of drugs, drug CSs also possess the ability to mimic the neurochemical effects of the drugs themselves on object memory consolidation. Supported by NSERC.

Role of nicotinic receptors in the perirhinal cortex in memory modulation by nicotine, cocaine, and their conditioned stimuli

Functional Magnetic Resonance Imaging (fMRI) and functional Near Infrared Spectroscopy (fNIRS) are neuroimaging techniques that can measure changes in blood flow in response to external stimuli. fNIRS is a portable imaging device and considered to be the optical equivalent of fMRI. The objective of this preliminary work is to investigate the ability of fNIRS to detect brain activity during a median nerve stimulation task in healthy controls and to compare the results to fMRI findings. To date, 25 healthy controls have been recruited to the fMRI task, of which 10 have also participated in the fNIRS task. Median nerve stimulation was conducted while brain activity was recorded with fMRI and fNIRS (tests done sequentially). Both the left and right hand were stimulated, successively, at a current that sustained thumb abduction (8-35 mA). A block design with eight cycles of stimulation 'on' and seven cycles of 'rest' was used. At the group level, for both fMRI and fNIRS, significant brain activity was observed in the contralateral primary and bilateral secondary somatosensory areas for each hand being stimulated. At the single subject level, the results demonstrate an 80% agreement between fMRI and fNIRS results where fMRI is considered ground truth. The overall good agreement between the two techniques is promising, and future work will focus on recruiting additional participants to better assess the sensitivity between modalities. Ultimately, this work adds to the growing body of research highlighting fNIRS as a suitable alternative to fMRI, as it affords the advantage of being portable and low-cost to maintain.

A quantitative comparison of fMRI and fNIRS activity to a median nerve stimulation task

The role of the hippocampus in representing space is widely supported. Neurons that increase their firing rate when an animal occupies a certain region, 'Place Cells,' have been thoroughly identified and studied in multiple species. This unique population of neurons has been thought to support a cognitive-map like representation of space in the brain; however, little is known about how these representations are formed in the common marmoset during free navigation in a 3D environment. Moreover, whether these representations are modulated by spatial view or movement kinematic has yet to be determined. In this work, we sought to identify the firing properties of neurons in the CA fields of the hippocampus while we register spatial and view information of freely navigating marmosets as they engage in a variety of foraging behaviors in 3D space. For this purpose, we habituated the experimental subjects to freely move inside a plexiglass recording chamber with four vertical levels while wearing affixed infrared reflective markers on top of skull implants that allowed for 6 degrees of freedom position and head direction camera tracking (Optitrack, Natural Point Inc, USA). Using MRI-guided neuro-navigation techniques, we chronically implanted 32ch microwire arrays in the hippocampus, and we were able to record single-unit activity during the aforementioned behaviors wirelessly. We analyzed data from 2 animals; spatial view and occupancy rate maps were constructed using 20cm3 bins. Spatial Information Content (SIC) was calculated independently for place and view for 200 total cells. SIC was higher for the spatial view than body position. We also found cells whose firing rate was highly correlated for both body velocity and head angular velocity.

Representation of 3D space in the hippocampus of freely moving marmosets

While the SARS-CoV-2 virus is well known for its impact on the respiratory system, neurological symptoms such as headache, anosmia, and cognitive impairments have been observed. Most strikingly, anosmia is reported in around 50% of COVID-19 cases. Male golden hamsters are used to study the outcomes of SARS-CoV-2 infection and therefore may also be used to model the neurological and behavioural effects of following virus challenge. To this end, we are developing a behavioural battery that could easily be run by any scientific group in containment level 3 to assess behavioral changes in hamsters following SARS-CoV-2 infection. All tasks rely on rodents' innate preference for novelty and are conducted without extensive training or rule learning. Briefly, hamsters are exposed to two copies of a stimulus (odour or object) in a training trial. Following a brief delay, the hamsters are re-exposed to a third copy of the now familiar stimulus, and a novel stimulus. Results indicate that hamsters show a preference for novel odours; however, they are unable to perform the object-based task. In a sociability task, male hamsters were found to preferentially explore a novel hamster more than a novel object, as well as discriminate between a novel and familiar hamster in a similar paradigm. Experiments to refine these tasks are ongoing, with a goal of incorporating them into SARS-CoV-2 vaccine trials at the Vaccine and Infectious Disease Organization/Intervac in the fall of 2021.

Development of spontaneous tests of olfactory, object, and social discrimination behaviour in male golden hamsters: use in rodent models of SARS-CoV-2 infection?

Investigating the influence of perineuronal nets surrounding parvalbumin-positive neurons in sensorimotor circuitry on motor performance

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