Our Projects

Our research aims to uncover neurobiological mechanisms through which the brain learns from predictive relationships in the environment and uses them to predict the future. We investigate the neural implementation of relational learning and inference with various cognitive tasks in rodents. By monitoring and manipulating the activity of brain cells, 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.

Neural implementation of memory transformation

To choose what to do, we use what we see in the present or know from the past. For the latter, we need to learn how things are connected and use that knowledge in new situations. We investigate the activity of a large group of neurons in the medial prefrontal cortex and the hippocampus during these knowledge construction and application processes to uncover their mechanisms at the level of millisecond-resolved neural ensemble dynamics.

Jarovi J, Pilkiw M, Takehara-Nishiuchi K, (2023) Prefrontal neuronal ensembles link prior knowledge with novel actions during flexible action selection. Cell Reports, 42, 113492
Takehara-Nishiuchi K, (2022) Flexibility of memory for future-oriented cognition. Current Opinion in Neurobiology 76:102622.
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.
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.

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

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