The effects of neuron diversity in a specific brain region on memory are still being studied. Neurons are the specialized cells in the brain that transmit and process information. There is a high degree of neuron diversity within a memory-related brain region, such as the hippocampus. Variations in the molecular properties of individual neurons, their connectivity patterns, or their functional roles can all contribute to this diversity.
Cornell researchers report in a new study that neurons in a key area of the brain have different functions based on their exact genetic identity, and understanding this diversity could lead to a better understanding of the brain’s computational flexibility and memory capacity, potentially informing disease treatment options.
Pyramidal cells in the hippocampus’s CA1 region, previously thought to be a uniform collection of neurons, have recently been discovered to be highly diverse. However, until now, the role of this diversity in cognitive functions had not been thoroughly investigated.
“Most memory studies assume the hippocampus and cortex are like black boxes – monolithic structures, homogeneous sets of neurons,” explained co-senior author Antonio Fernandez-Ruiz, assistant professor of neurobiology and behavior and Nancy and Peter Meinig Family Investigator in the Life Sciences in the College of Arts and Sciences (A&S). “Basically, you have two black boxes that communicate with each other, but you don’t know what these two boxes are made of.”
Hippocampo-Cortical Circuits for Selective Memory Encoding, Routing, and Replay. We discovered that these structures communicate in at least two different ways. There are also specialized circuits integrated by different cell types that encode various types of information and send it to different parts of the brain.
Azahara Oliva
“Hippocampo-Cortical Circuits for Selective Memory Encoding, Routing, and Replay” published in the journal Neuron. Co-senior author is Azahara Oliva, assistant professor of neurobiology and behavior (A&S).
In tests on rats, Fernandez-Ruiz and his colleagues discovered that CA1 neurons encode task-related information concurrently, but then send impulses to different targets depending on whether the neurons are deep in the hippocampus or on the surface.
“We discovered that these structures communicate in at least two different ways,” he explained. “There are also specialized circuits integrated by different cell types that encode various types of information and send it to different parts of the brain.”
The lab examined a large number of simultaneously recorded neurons in rats engaged in both memory tasks and sleep for their study, using high-density silicon probes. The probes detect cell encoding activity via synchronous oscillations known as sharp-wave ripples.
CA1 pyramidal cells (named for their shape) differed in some physiological properties depending on where they were located in the hippocampus (deep, middle, or superficial), as previously discovered. According to Fernandez-Ruiz, diversity is essential for memory development.
While deep CA1 pyramidal cells were the primary contributors to sequence and assembly dynamics, superficial cells were specifically recruited during the replay of novel experiences and drove memory formation.
“When you learn something new,” he said, “these aspects of experience can be segregated and encoded by specialized populations of neurons, then transmitted to different areas, which are specialized in processing different types of information. We believe this is important because this provides a system with more flexibility.”
The researchers also discovered a previously unknown memory consolidation circuit involving the hippocampus and cortex. According to Oliva, a better understanding of the hippocampus’s neuronal diversity could help target areas affected by dementia.
“A disease like Alzheimer’s is characterized by impairments of this communication between the hippocampus and the cortex,” she explained, “but we don’t know whether the entire structures are disrupted or, more likely, some specific neuron types in these structures are more affected. If you could determine which aspect of memory is disrupted,” she said, “you might be able to trace that back to the specialization of different cell types and perhaps employ new, more targeted therapies.”
