Posts tagged hippocampal neurons
Articles and news from the latest research reports.
Biologists pave the way for improved epilepsy treatments
University of Toronto biologists leading an investigation into the cells that regulate proper brain function, have identified and located the key players whose actions contribute to afflictions such as epilepsy and schizophrenia. The discovery is a major step toward developing improved treatments for these and other neurological disorders.
“Neurons in the brain communicate with other neurons through synapses, communication that can either excite or inhibit other neurons,” said Professor Melanie Woodin in the Department of Cell and Systems Biology at the University of Toronto (U of T), lead investigator of a study published today in Cell Reports. “An imbalance among the levels of excitation and inhibition – a tip towards excitation, for example – causes improper brain function and can produce seizures. We identified a key complex of proteins that can regulate excitation-inhibition balance at the cellular level.”
This complex brings together three key proteins – KCC2, Neto2 and GluK2 – required for inhibitory and excitatory synaptic communication. KCC2 is required for inhibitory impulses, GluK2 is a receptor for the main excitatory transmitter glutamate, and Neto2 is an auxiliary protein that interacts with both KCC2 and GluK2. The discovery of the complex of three proteins is pathbreaking as it was previously believed that KCC2 and GluK2 were in separate compartments of the cell and acted independently of each other.
“Finding that they are all directly interacting and can co-regulate each other’s function reveals for the first time a system that can mediate excitation-inhibition balance among neurons themselves,” said Vivek Mahadevan, a PhD candidate in Woodin’s group and lead author of the study.
Mahadevan and fellow researchers made the discovery via biochemistry, fluorescence imaging and electrophysiology experiments on mice brains. The most fruitful technique was the application of an advanced sensitive gel system to determine native protein complexes in neurons, called Blue Native PAGE. The process provided the biochemical conditions necessary to preserve the protein complexes that normally exist in neurons. Blue Native PAGE is advantageous over standard gel electrophoresis, where proteins are separated from their normal protein complexes based on their molecular weights.
“The results reveal the proteins that can be targeted by drug manufacturers in order to reset imbalances that occur in neurological disorders such as epilepsy, autism spectrum disorder, schizophrenia and neuropathic pain,” said Woodin. “There is no cure for epilepsy; the best available treatments only control its effects, such as convulsions and seizures. We can now imagine preventing them from occurring in the first place.”
“It was the cellular mechanisms that determine the excitation-inhibition balance that needed to be identified. Now that we know the key role played by KCC2 in moderating excitatory activity, further research can be done into its occasional dysfunction and how it can also be regulated by excitatory impulses,” said Mahadevan.
(Source: media.utoronto.ca)
New learning and memory neurons uncovered
A University of Queensland study has identified precisely when new neurons become important for learning.
Lead researcher Dr Jana Vukovic from UQ’s Queensland Brain Institute (QBI) said the study highlighted the importance of new neuron development.
“New neurons are continually produced in the brain, passing through a number of developmental stages before becoming fully mature,” Dr Vukovic said.
“Using a genetic technique to delete immature neurons in animal models, we found they had great difficulty learning a new spatial task.
“There are ways to encourage the production of new neurons – including physical exercise – to improve learning.
“The new neurons appear particularly important for the brain to detect subtle but critical differences in the environment that can impact on the individual.”
The study, performed in QBI Director Professor Perry Bartlett’s laboratory, also demonstrates that immature neurons, born in a region of the brain known as the hippocampus, are required for learning but not for the retrieval of past memories.
“On the other hand, if the animals needed to remember a task they had already mastered in the past, before these immature neurons were deleted, their ability to perform the task was the same – so, they’ve remembered the task they learned earlier,” Dr Vukovic said.
This research allows for better understanding of the processes underlying learning and memory formation.
(Image Caption: Newly generated neurons doublecortin positive in the dentate gyrus of a degenerating hippocampus in mutant mice lacking the transcription factor TIF-IA. Credit: Rosanna Parlato (AG Schütz, DKFZ-ZMBH Alliance)
Relating the function of neuronal cell types to information processing and behavior is a central goal of neuroscience. In the hippocampus, pyramidal cells in CA1 and the subiculum process sensory and motor cues to form a cognitive map encoding spatial, contextual, and emotional information, which they transmit throughout the brain. Do these cells constitute a single class or are there multiple cell types with specialized functions? Using unbiased cluster analysis, we show that there are two morphologically and electrophysiologically distinct principal cell types that carry hippocampal output. We show further that these two cell types are inversely modulated by the synergistic action of glutamate and acetylcholine acting on metabotropic receptors that are central to hippocampal function. Combined with prior connectivity studies, our results support a model of hippocampal processing in which the two pyramidal cell types are predominantly segregated into two parallel pathways that process distinct modalities of information.