Canada

Major depressive disorder (MDD) will affect 20% of individuals and is now considered the leading cause of disabilities worldwide. However, most studies still investigate MDD exclusively in males. We reported that chronic social stress induces blood-brain barrier (BBB) leakiness through loss of tight junction protein claudin-5 (cldn5) in the nucleus accumbens (NAc), a mood regulation center, of male mice allowing the passage of circulating inflammatory mediators into the brain and establishment of depression-like behaviors. In rodents, exposure to chronic social defeat stress (CSDS) through physical encounter with a larger aggressive mouse induces a depression-like phenotype. A subpopulation of mice does not develop depressive behaviors and is considered resilient, allowing us to also study biological adaptations promoting stress resilience. After CSDS, cldn5 gene expression is unchanged in the NAc of stress-susceptible females but decreased in the prefrontal cortex (PFC), a brain region regulating decision making and social behaviors, when compared to controls and resilient mice. This sexual dimorphism of stress-induced neurovascular adaptations was confirmed in post-mortem human brain samples from depressed individuals, adding translational value to our findings. Viral-mediated functional manipulation confirmed the causality of cldn5 loss in the female PFC in the establishment of depressive behaviors and possibly sex-specific MDD symptomatology. This data suggests that stress-induced neurovascular changes do not occur in the same brain regions in stressed females vs males.

CAN-ACN 2021

Sex-specific blood-brain barrier alterations and vascular biomarkers underlie chronic stress responses in mice and human depression

major depressive disorder

blood-brain barrier

sex differences

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

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.

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

With the recent legalization of cannabis in Canada, there is concern that its use may perpetuate negative outcomes in mental health and impact executive brain functions like working memory (WM). The endocannabinoid (eCB) system regulates the homeostasis of the circuitry underlying memory processes. We were interested in investigating the effects of acute cannabis smoke (Mohawk strain, high-THC; Treasure Island strain, low-THC) exposure on adult male Long-Evans rats' WM capacity. We used a validated object paradigm to evaluate visuospatial WM capacity. Then, we developed a novel odour-based paradigm for assessing olfactory WM capacity as it is rodents' primary sense. An identical (IOT) and differential (DOT) version of the paradigms allowed us to evaluate various cognitive loads on WM capacity using 3 and 6 items. The spontaneous WM tasks used capitalize on rodents' innate preference for novelty and the time spent exploring familiar stimuli in the sample phase, and novel stimuli introduced in the test phase, was analyzed. In both the object and odour paradigms, a load-dependent effect on memory was found whereby more stimuli notably decreased WM function in the DOT, but not IOT, versions. Following acute smoke exposure, no overall disruption in WM function was observed in the object paradigm. However, WM deficits were observed in the odour paradigm after acute exposure to Mohawk, but not Treasure Island, smoke in both the IOT and DOT task. Due to this olfaction-based WM disruption, the task shows promise to model the cognitive impacts of cannabis consumption in humans.

Use of spontaneous object- and odour-based working memory (WM) tasks to evaluate the effects of acute cannabis smoke exposure on WM capacity in male rats

It has been hypothesized that cell assemblies represent mental or perceptual entities, forming the basis of neural coding and computation. We investigated how the number of cell assemblies was related to the age of the rats and spontaneous remapping, using unit recordings of CA1 pyramidal cells in six young and six old rats while they learned a place-dependent eyeblink conditioning task (Schimanski et al., 2013). To control the dependence of cell assembly detection on different number of recorded neurons, we selected 30 pyramidal cells randomly from each recording session and repeated the procedure 25 times. This generated >8000 data sets. The number of cell assemblies was estimated by a recently proposed method (Russo and Durstewitz, 2017). We found that young rats had significantly more cell assemblies than old ones (median for young = 166.7, median for old = 87.4, Mann-Whitney test, p = 3.1 x 10-8). Significantly more cell assemblies were also detected in non-remapping rats than remapping ones (median for non-remapping = 192.1, median for remapping = 90.9, Mann-Whitney test, p = 8.4 x 10-13). Interestingly, cell assemblies were most abundant in the first few days of recording if rats were grouped into non-remapping, young or old, but not in remapping. Taken together, we showed that significantly more cell assemblies were detected in young and non-remapping rats. Reduction of cell assemblies over training in non-remapping rats suggests that efficient neural codes may be generated by learning and hence a reduced number of cell assemblies is sufficient.

Hippocampal CA1 network supports more cell assemblies in young and non-remapping rats

Behavioural neuroscience researchers continue to seek relevant rodent paradigms that mimic human patterns of cannabis use. Injected Δ9-tetrahydrocannabinol (THC) is commonly used to assess acute cannabis effects in rodents despite pharmacokinetics varying greatly between injection and inhalation. In addition, tasks used to assess behaviour following cannabis exposure often lack strong translational relevance to human tasks. Therefore, in the present experiment, we investigated cognitive effects of acute exposure to cannabis smoke in two rodent tasks highly translatable to human tasks for measuring working memory, attention, and impulsivity. Male Long-Evans rats were trained in two cognitive tasks using touchscreen-equipped operant conditioning chambers: (1) the trial-unique, delayed nonmatching-to-location (TUNL; n=16); (2) the five-choice serial-reaction time task (5CH; n=16). Trained rats received: (i) combusted cannabis smoke (two strains: Mohawk, high-THC; Treasure Island: low-THC) using a 4-chamber pump-driven system; or (ii) injected THC (3.0mg/kg; i.p.) and behaviour was immediately assessed on the tasks. Interestingly, we failed to observe any effects of cannabis smoke on performance of TUNL or 5CH; however, injected THC significantly reduced accuracy and number of trials completed during TUNL, plus a notable (albeit insignificant) increase in omissions during 5CH. These data support a growing literature showing distinct differences between cannabis strain and method of administration, highlighting a continued need to investigate cannabinoid effects on cognition.

Effects of smoked cannabis and injected Δ9-tetrahydrocannabinol on touchscreen-based tasks for measuring working memory, attention, and impulsivity in male Long Evans rats

The functioning of timbre and other form-bearing dimensions in music depends on the acoustic generation of sound, as well as physiological responses and the psychological organization of the information carried by sound. Human hearing can be reshaped by individual experience and can even be affected by cultural circumstances. To understand how hearing loss can affect the perception of timbre, we adopted noise maskers of varying kinds into a one-interval 2AFC task measuring the performance of timbre identification. Stimuli were presented using participant's personal laptop over headphones/earphones. In each trial, either a 300-ms trumpet or clarinet note at 440-Hz fundamental (target) with the same pitch was embedded in the middle of a 1-second Gaussian noise (masker). Three types of noise were used: broad-band noise, low-pass noise filtered at 4 kHz, and band-pass noise filtered between 5 kHz and 9 kHz. The target was fixed at one sound level, while the maskers of each kind were attenuated to 3 different levels. Our preliminary results show that (1) performance on the timbre identification task can be undermined by increasing the masker level and (2) noise maskers through a low-pass filter are as effective as broadband noise maskers but not those through a band-pass filter, suggesting that lower frequencies contribute more to identification. In future studies, we will further refine the composition of the noise masker, in both spectral and temporal domains, to explore how acoustic features contribute to timbre perception.

Identification of musical instrument sounds under noise masking

The cortical mechanisms for presaccadic signal processing remain poorly understood at the network level, in particular how they interact with simultaneously presented visual stimuli. Here, we used graph theory analysis (GTA) to construct and evaluate functional brain networks based on EEG data collected in the perisaccadic interval. EEG was recorded via 64 channels in two behavioral conditions (fixation or saccade). Participants (N=21) were pre-cued with a series 1-3 grids (three horizontal lines, 10° by 10°) located 5° below the central fixation-point. 100ms later, a stimulus (three vertical lines; same size/location) was briefly presented (for 70ms). In the saccade condition, a left/right shift of the fixation-point during the interstimulus interval triggered a saccade after the second stimulus. Source localization (SL) was performed on the 200ms period following the saccade cue, or the equivalent time during fixation trials. Lagged coherences were calculated between all pairs of 84 Brodmann areas. SL/GTA identified major network hubs near the frontal and parietal eye fields, with widespread cortical connectivity. Other GTA measures (clustering coefficient, global efficiency, energy, entropy) showed that network segregation, integration, synchronizability, and complexity were enhanced during the perisaccadic interval. Further, these network properties significantly interacted with stimulus repetition, altering both hubs and network topography. These data suggest a network mechanism for enhanced visual information processing and propagation in the presaccadic interval. Acknowledgements: Grant Support: an NSERC Discovery Grant and VISTA Fellowship, funded by CFREF.

Functional brain network for presaccadic visual processing: evidence from high resolution EEG and graph theory analysis

The diagnosis of concussion remains challenging, particularly in cases where several months have passed between a head injury and clinical assessment. Tracking multiple moving objects in three-dimensional (3D) space engages many of the same cognitive processes that are affected by concussion, a form of mild traumatic brain injury (mTBI), suggesting that tests of 3D multiple object tracking (3D-MOT) may be sensitive to post-concussion syndrome after a brain injury has occurred. To test this, we evaluated 3D-MOT performance (using NeuroTrackerTM) against Sports Concussion Assessment Tool results for cognition, balance, and symptom severity in a large sample (N = 457) of male and female participants between the ages of 6 to 73. 3D-MOT performance in subjects under age 13 was not impaired by a history of concussion, but was positively associated with cognition and balance. 3D-MOT performance in those 13 and older was negatively associated with concussion symptom severity, and positively associated with cognition and balance. 3D-MOT was selectively impaired in subjects with probable post-concussion syndrome (pPCS), defined using the 95th percentile of symptom severity for subjects with no history of concussion. A decision tree predicted concussion status with 95.2% overall test accuracy (91.1% sensitivity, 97.8% specificity) using concussion history, age, and 3D-MOT score. Individuals with a history of concussion in the past 37 days were predicted to have pPCS if they were age 35 or older, or if they were under age 35 but achieved scores below 1.2 on the 3D-MOT. These results demonstrate the potential of 3D-MOT for pPCS diagnosis, and highlight the increased vulnerability to concussion symptoms that comes with age.

Multiple object tracking scores predict post-concussion status years after mild traumatic brain injury

Parvalbumin (PV) expressing neurons are a subclass of inhibitory cells that strongly regulate the activity of local excitatory neurons. PV neurons are important for maintaining excitation balance in the cortex and are involved in generating synchronous high frequency neuron firing. In the prefrontal cortex (PFC), disrupting the activity of PV neurons is associated with various cognitive impairments. The goal of this study was to assess the role of prefrontal PV neurons during focused visual attention in mice. We used the touchscreen rodent continuous performance task, which allows us to study various aspects of attention, including sustained attention, impulsivity, and visual discrimination. In vivo calcium imaging revealed that PFC PV neurons display increased activity prior to responding to the correct stimulus that increases through training. In vivo optogenetics was used to inactivate PFC PV neurons, or stimulate these neurons at a high (30hz) or low (5hz) frequency during the response phase of the task. When PV neurons were either inactivated or stimulated at 5hz, the animals' ability to attend to a target image was significantly reduced. Alternatively, stimulating PV neurons at 30hz significantly improved the animal's ability to attend to and discriminate the correct image, demonstrating a frequency specific bi-directional effect of PV stimulation. We also observe that an animal's baseline performance (high or low) is predictive of whether optogenetic manipulation can impair or enhance task performance, respectively. This implies that the effectiveness of optogenetic stimulation on altering attention may depend on the baseline organization of PFC activity, and that animals with unoptimized PFC function can be improved by high frequency stimulation of PV neurons.

Prefrontal parvalbumin neurons facilitate the acquisition and performance of attention in mice

The presence of an allocentric landmark can have both explicit (instruction-dependent) and implicit influences on reaching performance (Byrne and Crawford 2010; Chen et al., 2011; Klinghammer et al. 2015, 2017). However, it is not known how the instruction itself (to rely either on egocentric versus allocentric cues) influences memory-guided reaching. Here, 13 participants performed a task with two instruction conditions (egocentric vs. allocentric), but with similar sensory and motor conditions. In both conditions, participants maintained fixation while a LED target briefly appeared (alongside a visual landmark) in one visual field. After a mask/memory delay period, the landmark re-appeared in the same or opposite visual field. In the allocentric condition, participants were instructed remember the initial location of the target relative to the landmark, and to reach relative to the shifted landmark. In the egocentric condition, subjects were instructed to ignore the landmark and point toward the remembered location of the target (50% of trials were motor-matched anti-reaches). The allocentric instruction yielded significantly more accurate pointing than the egocentric instruction, despite identical visual and motor conditions and regardless of the final pointing side. These results show that memory-guided pointing improves when participants are explicitly instructed to point relative to the landmark. This suggests that explicit attention to a visual landmark recruits allocentric coding mechanisms that are more resistant to memory decay than egocentric mechanisms.

Explicit attention to allocentric visual landmarks improves memory-guided reaching

As we read, communication across brain networks allows us to integrate the way words look, sound, and mean. Phonological (sounds) and semantic (meaning) processing are key components of skilled reading. Understanding their underlying neural systems in adults sets a foundation to explore their development in children. In this pilot study, 64-channel EEG was recorded while adults (n=14; ages=23-36; 8 male) read word pairs that were rhyming or nonrhyming (goose-juice vs. small-juice) and semantically related or unrelated (open-close vs. nest-close). The goal was to explore both the event related potentials (ERPs) associated with lexical access (the N400) and oscillatory power effects associated with brain network integration during both types of priming. While similar N400 effects were seen for both phonological and semantic priming (larger N400 for unrelated vs. related words at central/mid-line electrodes 300-550ms; ps<.001), the frequency and duration of oscillatory power effects differed. Phonologically unrelated vs. related words showed greater power in beta (13-30 Hz, 334-820ms, p<.05), and gamma (31-80Hz, 292-456ms, p<.001), while semantically unrelated vs. related words showed greater long-lasting power in theta (4-7 Hz, 42-2400ms, p<.05), alpha (8-12 Hz, 122-1040ms, p<.05) and beta (13-30 Hz, 878-1544ms and 1944-2500ms, ps<.05). In line with speech processing models, higher frequency oscillations may be associated with sound as compared to meaning processing. Oscillatory power may reveal additional insights into the brain networks important for reading than ERPs alone.

Sex-specific blood-brain barrier alterations and vascular biomarkers underlie chronic stress responses in mice and human depression

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