Most things are what they are, no matter what their genesis. For calcium though, provenance matters. This is the take-home from a recently published study from Dr. Suhita Nadkarni’s group at IISER Pune in which the team has investigated if and how calcium ions from different sources impact memory in unique ways. This work was carried out in collaboration with researchers from Salk Institute for Biological Studies and Rice University.
How are memories formed, stored and retrieved? What is the sub-cellular basis of various forms of memory? How do neurons talk to each other and how does one quantify the strength of connections between neurons? Intriguing questions such as these are being addressed in the field of Neuroscience.
Synapse, a narrow gap at the end of a neuron, is a busy location for neuronal signaling. The calcium levels within the neuron, along with other cues, direct the release of neurotransmitters into the synapse, thus initiating the signal, followed by passing on the signal to the next neuron.
The spatiotemporal characteristics, that is, the when-and-where details, of the calcium signal in the synapse precisely govern all kinds of short-lived and long-lasting memories. The short-lived memory type, for example working memory, retains information from milliseconds to minutes. This type of memory is critical for making real-time decisions involved in navigating, reading comprehension, or something as simple as finding a lost object--the reason you don’t keep opening the same drawer over and over again to find your lost pen.
Several sources and sinks of calcium are available to the synapse, each activated by a distinct trigger, that turn-on and turn-off at different times. “The contribution of each source to specific types of memory is yet unknown. This is partly because experiments that directly measure calcium concentrations within tiny synaptic spaces are extremely difficult to do,” says Dr. Nadkarni, whose group employs computational approaches to understand synaptic transmission.
The team overcame these practical hurdles using in-silico experiments that modelled synapses of the hippocampus (memory-center of the brain) that were meticulously reconstructed on a computer from images of brain slices. Their motivation was to understand how each calcium source uniquely impacted memory.
Describing the results obtained, PhD student Nishant Singh says, “Our work showed that the endoplasmic reticulum (ER), a calcium-rich intracellular organelle, strengthens synaptic connections over time-scales that are relevant for working memory. In fact, other studies have shown that when the ER is blocked in normal synapses, they behave much like synapses in brains afflicted by Alzheimer’s disease.”
The team concludes that this work points to a causal link between changes in calcium signalling due to a malfunctioning ER, reduced strengths of synaptic connections, and deficits in working memory that are a characteristic of Alzheimer’s disease.
This research was supported by funds from DBT/Wellcome Trust India Alliance and IISER Pune.
Nishant Singh, Thomas Bartol, Herbert Levine, Terrence Sejnowski and Suhita Nadkarni (2021). Presynaptic endoplasmic reticulum regulates short-term plasticity in hippocampal synapses. Communications Biology Volume 4, Article Number: 241
- With inputs from Suhita Nadkarni and Nishant Singh