A novel instructive role for the entorhinal cortex discovered

A longstanding question in neuroscience is how mammalian brains (including ours) adapt to external environments, information, and experiences. In a paradigm-shifting study published in Nature, researchers at the Jan and Dan Duncan Neurological Research Institute (Duncan NRI) at Texas Children’s Hospital and Baylor College of Medicine have discovered the mechanistic steps underlying a new type of synaptic plasticity called behavioral timescale synaptic plasticity (BTSP). The study, led by Dr. Jeffrey Magee, professor at Baylor, who is also a Howard Hughes Medical Institute, and Duncan NRI investigator, reveals how the entorhinal cortex (EC) sends instructive signals to the hippocampus — the brain region critical for spatial navigation, memory encoding, and consolidation — and directs it to specifically re-organize the location and activity of a specific subset of its neurons to achieve altered behavior in response to its changing environment and spatial cues.

Neurons communicate with one another by transmitting electrical signals or chemicals through junctions called synapses. Synaptic plasticity refers to the adaptive ability of these neuronal connections to become stronger or weaker over time, as a direct response to changes in their external environment. This adaptive ability of our neurons to respond quickly and accurately to external cues is critical for our survival and growth and forms the neurochemical foundation for learning and memory.

An animal’s brain activity and behavior adapt quickly in response to spatial changes

To identify the mechanism that underlies the mammalian brain’s capacity for adaptive learning, a postdoctoral fellow in the Magee lab and lead author of the study, Dr. Christine Grienberger, measured the activity of a specific group of place cells, which are specialized hippocampal neurons that build and update ‘maps’ of external environments. She attached a powerful microscope to the brains of these mice and measured the activity of these cells as the mice were running on a linear track treadmill.

In the initial phase, the mice were acclimated to this experimental setup and the position of the reward (sugar water) was altered at each lap. “In this phase, the mice ran continuously at the same speed while licking the track continuously. This meant the place cells in these mice formed a uniform tiling pattern,” said Dr. Grienberger who is currently an assistant professor at Brandeis University.

In the next phase, she fixed the reward at a specific location on the track along with a few visual cues to orient the mice and measured the activity of the same group of neurons. “I saw that changing the reward location altered the behavior of these animals. The mice now slowed down briefly before the reward site to taste the sugar water. And more interestingly, this change in behavior was accompanied by increased density and activity of place cells around the reward site. This indicated that changes in spatial cues can lead to adaptive reorganization and activity of hippocampal neurons,” Dr. Grienberger added.

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