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The overarching goal of our research is to uncover neurobiological mechanisms through which intelligent behavior emerges from memory. We investigate the neural implementation of knowledge construction, updating, and application using various cognitive tasks that test contingency learning, relational memory, and inference. By monitoring and manipulating the activity of brain cells in freely behaving rodents, we connect these cognitive processes with real-time dynamics in neural ensembles and circuits. In parallel, we use the fundamental principles of neural dynamics to probe the pathophysiology underlying cognitive deficits in mental disorders.

Neuronal implementation of memory transformation

Detected event relationships should be stored as stable memorie traces so that we can use them to adaptively behave in the future.  Some relationships may be stored with their surrounding contextual details while others may be combined with similar ones and become generalizable abstraction of the world. We study how the hippocampus and medial prefrontal cortex interact through the rhinal cortex and midline thalamic regions to maintain this balance between abstraction and detail.

  1. Xing B, Morrissey MD, Takehara-Nishiuchi K, (2020) Distributed representations of temporal stimulus associations across regular-firing and fast-spiking neurons in rat medial prefrontal cortex, J Neurophysiology, 123(1): 439-450. 

  2. Morrissey M, Insel N, Takehara-Nishiuchi K. (2017) Generalizable knowledge outweighs incidental details in prefrontal ensemble code over time. eLife, 6:e22177. Featured on more than 20 news websites, including Neuroscience News, ScienceDaily, and U of T Bulletin.

Neuronal dynamics supporting selective memory encoding

Capturing the most relevant information from everyday experiences without constantly learning unimportant details is vital to survival and mental health. One factor that controls this selection process is the similarity between the current situations and past experiences. Specifically, new information can be encoded rapidly if it is congruent to prior knowledge of latent patterns, categories, and rules. We study the role of the medial prefrontal cortex in this fast-track memory encoding.

  1. Takehara-Nishiuchi K, Morrissey MD, Pilkiw M (2020) Prefrontal neural ensembles develop selective code for stimulus associations within minutes of novel experiences, J Neurosci, 40(43): 8355-8366.

  2. Takehara-Nishiuchi K, (2020) Prefrontal-hippocampal interaction during the encoding of new memories, Brain and Neuroscience Advances, 4: 1-10.

  3. Jarovi J, Volle J, Yu XT, Guan L, Takehara-Nishiuchi K, (2018) Prefrontal theta oscillations promote selective encoding of behaviorally relevant events, eNeuro, 5(6) e0407-18.

  4. Volle J, Yu XT, Sun H, Tanninen SE, Insel N, Takehara-Nishiuchi K. (2016) Enhancing prefrontal neuron excitability enables associative learning of temporally disparate events. Cell Reports, 15(11):2400-2410.

Function of the lateral entorhinal cortex in memory and memory disorders

The entorhinal cortex (EC) serves as an interface between the hippocampus and neocortex and consists of the medial and lateral areas with dissociable anatomical connectivity. We study the role of its lateral portions (LEC) in memories of event-context associations. Our focus is how disrupted LEC affects memory processing in other brain regions to gain insight into mechanisms of memory problems in elderly and Alzheimer's disease patients with the degenerated LEC.

  1. Nouriziabari, SB, Sarkar S, Tanninen SE, Dayton R, Klein RL, Takehara-Nishiuchi K. (2018) ERP-based detection of brain pathology in rat models for preclinical Alzheimer’s disease. Journal of Alzheimers Disease, 63(2): 725-740.

  2. Pilkiw M, Insel N, Cui Y, Finney C, Morrissey MD, Takehara-Nishiuchi K. (2017) Phasic and tonic neuron ensemble codes for stimulus-environment conjunctions in the lateral entorhinal cortex, eLife, 6, e28611.  

  3. Tanninen SE, Nouriziabari, SB, Morrissey MD, Bakir R, Dayton R, Klein RL, Takehara-Nishiuchi K. (2017) Entorhinal tau pathology induces a neuronal signature in preclinical stages of Alzheimer’s disease. Neurobiology of Aging, 58:151-162.

  4. Takehara-Nishiuchi K. (2014) Entorhinal cortex and consolidated memory. Neuroscice Research, 84C:27-33.

  5. Morrissey MD, Maal-Bared G, Brady S, Takehara-Nishiuchi K (2012) Functional dissociation within the entorhinal cortex for memory retrieval of an association between temporally discontinuous stimuli. Journal of Neuroscience, 32(16), 5356-5361. 

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