My research is broadly interested in the role that non-cellular mechanisms play in long-term memory formation and persistence. I am especially interested in extracellular matrix structures called perineuronal nets (PNNs). PNNs are known for ushering in the end of juvenile-like plasticity during development. In adulthood, condensed extracellular matrix structures, including PNNs, are found around neuron cell bodies and other notable subcellular compartments, like the axon initial segment. They have been shown to be necessary for LTM; however, their exact function is not known. Our lab uses olfactory memory as a model for investigating the function of PNNs in LTM.
Current & Ongoing projects
🦠 Steifman C*, Lagasse O*, Tonc E, Iwasaki A, Lu P, Monje M, Tong MT. Investigating Microglia-Mediated Loss of Hippocampal Perineuronal Nets in Mild Respiratory COVID.
🦵🏽 Pineda J*, Allodi I, Tong MT. Investigating the Role of Spinal Cord Perineuronal Nets during Amyotrophic Lateral Sclerosis Disease Progression.
💊 Tong MT, Bates S. Perineuronal Net Responses to Benzodiazepine Addiction and Withdrawal.
🪀 Werth J, Gacy T*, Lee P*, Richardson T*, Maclin J*, Davis S*, Cleland TA, & Tong MT. Removal of Perineuronal Nets in the Olfactory Bulb Decreases Spike-timing Variability and Attenuates Gamma Power.
Animals rely on memory representations of their sensory environment to inform survival behaviours. At the neuronal level, the specificity of memory representations corresponds to long-lasting changes within neural circuits in response to behaviourally relevant experiences. Recently, perineuronal nets (PNNs) have received increased attention as a potential memory mechanism due to their necessity for long-term memory (LTM) persistence and activity-dependent expression around inhibitory interneurons. Together, the studies show that the neurons which become ensheathed by PNNs after learning play critical roles within neural circuits for the shaping of memory representations. In this study, we investigate odour-evoked expression and function of PNNs in the mouse main olfactory bulb (MOB) circuit using an in vitro microelectrode array olfactory bulb prep where artificial odours are optogenetically “played” onto olfactory sensory neurons.
📊 Choi S*, Houlihan M*, Gurupusad R*, Lo C*, & Tong MT. Extracellular Matrix is Necessary for the Persistence of Olfactory Perceptual Learning.
Traditional memory experiments use test/pre-test comparisons of latency or proportion correct as metrics of memory retention. While these metrics can effectively assess differences in memory between time points, they fail to provide insight into the underlying representations responsible for observed memory differences. Observed memory deficits using traditional measures can arise from representations with reduced strength or reduced specificity.
We are using the olfactory generalization task to measure the shape of the odor representation associated with reward (Cleland et al., 2021) while we manipulate PNN expression in the olfactory bulb with a modified adeno-associated virus (AAV) which targets chondroitinase ABC (an enzyme that digests PNNs) to specific neuronal populations using the Cre-LoxP system.
🤯 Yang L*, Hughes S, Tong MT. Decolonizing neuroscience in practice.
While ideas of “decolonizing” curriculum and pedagogy in higher education have been gaining traction in recent years, efforts to implement meaningful curricular changes have been primarily in the humanities and social science. A recent global, comparative review of 207 articles and book chapters on decolonizing curriculum found a notable absence of contributions from the STEM (Science, Technology, Engineering, and Mathematics) disciplines. As enrollment in STEM disciplines and national investment in the STEM workforce continue to rise, the STEM classroom is an important site of meaningful decolonizing interventions. Thus, the development of decolonizing materials and its implementation in STEM courses deserve critical examination. In this study, we seek to evaluate the effectiveness of an experimental curriculum intentionally designed for neuroscience students to engage with decolonial ideas of their field. Using interviews, a focus group, and pre-/post-course surveys, we examine (a) the effect of the curriculum on students’ sense of self-efficacy in their field and their sense of social belonging in the science classroom; (b) the efficacy of the implementation across 4 previously described implementation categories (probing the positionality of knowledge, constructing an inclusive curriculum, relational teaching and learning, and bridging higher education institutions with community and/or sociopolitical movements.)
PUBLISHED PROJECTS
🍫 Mudra Rakshasa, A*, & Tong, MT. (2020). Making Good Choices: Social Interaction in Mice Mitigates Chronic Stress-Induced Adaptive Changes in Decision Making. Frontiers in Behavioral Neuroscience, 14:81. [Article Link] [bioRxiv][Data Repository][Arish’s amazing Twitter paper summary thread]
Chronic stress can impact decision-making and lead to a preference for immediate rewards rather than long-term payoffs. Factors that may influence these effects of chronic stress on decision-making are under-explored. Here we used a mouse model to investigate the changes in decision-making caused by the experience of chronic stress and the role of social isolation in exaggerating these changes. To test decision-making, mice were trained to perform a Cost-Benefit Conflict (CBC) task on a T-maze, in which they could choose between a high-reward, high-risk alternative and a low-reward, low-risk alternative. Mice were either housed in groups or alone throughout the experiment. Both groups of mice underwent a seven-day period of repeated immobilization to induce chronic stress. Stress levels were confirmed using behavioral (open field test) and physiological (urine corticosterone ELISA) measures. We found a significant increase in frequency of high-risk decisions after exposure to chronic stress among both socially- and individually-housed mice. Crucially, socially-housed mice showed a significantly smaller increase in high-risk decision-making compared to singly-housed mice. These findings suggest that chronic stress leads to an increase in high-risk decision-making in mice, and that lack of social interaction may exacerbate this stress effect.
🐭 Awol, AK*, & Tong MT. (2020). A low-cost, odor-reward association task for tests of learning and memory. Journal of Visualized Experiments. (159), e59756. [Article Link]
Robust and simple behavioral paradigms of appetitive, associative memory are crucial for researchers interested in cellular and molecular mechanisms of memory. In this paper, an effective and low-cost mouse behavioral protocol is described for examining the effects of physiological manipulation (such as the infusion of pharmacological agents) on the learning rate and duration of odor-reward memory. Representative results are provided from a study examining the differential role of tyrosine kinase receptor activity in short-term (STM) and long-term memory (LTM). Male mice were conditioned to associate a reward (sugar pellet) with one of the two odors, and their memory for the association was tested 2 or 48 h later. Immediately prior to the training, a tyrosine kinase (Trk) receptor inhibitor or vehicle infusions were delivered into the olfactory bulb (OB). Although there was no effect of the infusion on the learning rate, blockade of the Trk receptors in the OB selectively impaired LTM (48 h), and not short-term memory (STM; 2 h). The LTM impairment was attributed to the diminished odor selectivity as measured by the length of the digging time. The culmination of the results of this experiment showed that Trk receptor activation in the OB is the key in olfactory memory consolidation.
🐟 Schroeder MK*, Tong MT, & Rosenberg RL. (2019). The effects of Curcumin on glial morphology following spinal cord injury in lampreys. IMPULSE. [Article Link ]
Reactive and consequently scar-forming glial cells, particularly astrocytes, are implicated in the inability of mammalian spinal cords to regenerate following spinal cord injury (SCI). Thus, it is relevant to study pharmacological methods of manipulating these cells, which could result in efficacious treatments for SCI in humans. The current study used larval sea lampreys (Petromyzon marinus), because lampreys can functionally recover from a spinal cord transection, making them a relevant model organism for studying how the process of physiological recovery may be sped up. Lampreys were given either a single injection of 27 μM curcumin, an established anti-inflammatory compound, or a vehicle not containing curcumin immediately following spinal cord transection and allowed to recover for 24 hours or one week. To assess the effects of curcumin on glial cells, spinal cord slices were labeled with an anti-cytokeratin antibody, LCM29, that labels lamprey glial cytoskeleton. There were no significant differences in immunoreactivity of the LCM29 antibody between vehicle- and curcumin-injected groups as measured by mean pixel value, or as measured by the standard deviations of these means. Despite the overall lack of significant main effects of curcumin according to these quantitative measures, there were distinct visual differences between spinal cord slices from curcumin- and vehicle-injected animals. While curcumin did not affect the overall levels of glial filaments, it may affect the uniformity of location of these filaments by attenuating the development of darker patches (decreased expression of glial filaments) and brighter patches (increased expression of glial filaments) seen in slices from vehicle-injected lampreys. Future studies should continue investigating curcumin for its ability or inability to attenuate reactive glial cells and explore new methods for quantifying glial reactivity.
⚡Tong, MT, Kim, PT-Y.*, & Cleland, TA. (2018). Kinase activity in the olfactory bulb is required for odor memory consolidation. Learning and Memory, 25, 198-205. [Article Link]
Long-term fear memory formation in the hippocampus and neocortex depends upon brain-derived neurotrophic factor (BDNF) signaling after acquisition. Incremental, appetitive odor discrimination learning is thought to depend substantially on the differentiation of adult-born neurons within the olfactory bulb (OB)—a process that is closely associated with BDNF signaling. We sought to elucidate the role of neurotrophin signaling within the OB on odor memory consolidation. Male mice were trained on odor–reward associative discriminations after bilateral infusion of the kinase inhibitor K252a, or vehicle control, into the OB. K252a is a partially selective inhibitor of tyrosine kinase (Trk) receptors, including the TrkB receptor for BDNF, though it also inhibits other plasticity-related kinases such as PKC and CaMKII/IV. K252a infusion into the OB did not impair odor acquisition or short-term (2 h) memory for the learned discriminations, but significantly impaired long-term (48 h) odor memory (LTM). This LTM deficit also was associated with reduced selectivity for the conditioned odorant in a reward-seeking digging task. Infusions of K252a immediately prior to testing did not impair LTM recall. These results indicate that kinase activation in the OB is required for the consolidation of odor memory of incrementally acquired information.
📜 Tong, MT, Peace, ST, and Cleland, TA (2014). Molecular and structural mechanisms of olfactory bulb memory. Frontiers in Behavioral Neuroscience, 8, 238. [Article Link]
Memories are dynamic physical phenomena with psychometric forms as well as characteristic timescales. Most of our understanding of the cellular mechanisms underlying the neurophysiology of memory, however, derives from one-trial learning paradigms that, while powerful, do not fully embody the gradual, representational, and statistical aspects of cumulative learning. The early olfactory system—particularly olfactory bulb—comprises a reasonably well-understood and experimentally accessible neuronal network with intrinsic plasticity that underlies both one-trial (adult aversive, neonatal) and cumulative (adult appetitive) odor learning. These olfactory circuits employ many of the same molecular and structural mechanisms of memory as, for example, hippocampal circuits following inhibitory avoidance conditioning, but the temporal sequences of post-conditioning molecular events are likely to differ owing to the need to incorporate new information from ongoing learning events into the evolving memory trace. Moreover, the shapes of acquired odor representations, and their gradual transformation over the course of cumulative learning, also can be directly measured, adding an additional representational dimension to the traditional metrics of memory strength and persistence. In this review, we describe some established molecular and structural mechanisms of memory with a focus on the timecourses of post-conditioning molecular processes. We describe the properties of odor learning intrinsic to the olfactory bulb and review the utility of the olfactory system of adult rodents as a memory system in which to study the cellular mechanisms of cumulative learning.