Opens up development of better drug for neural malfunctioning
Vienna, Austria/Thiruvananthapuram, India (ISJ) — Every time we learn something new, it registers in our brain ? a process that involves acquiring and stabilising, which means memorizing.
Brain waves are considered to play an important role in this process, but the underlying mechanism that dictates their shape and rhythm was still unknown. A study now published in Neuron shows, one of the brain waves important for consolidating memory is dominated by synaptic inhibition.
The new study at the Institute of Science and Technology Austria (IST Austria), found the mechanism that generates this oscillation of neuronal activity in mice. ?Our results shed light on the mechanisms underlying this high-frequency network oscillation. As our experiments provide information both about the phase and the location of the underlying conductance, we were able to show that precisely timed synaptic inhibition is the current generator for sharp wave ripples.? explained author Professor Peter Jonas.]
?Understanding spatial manipulation of such waves would surely enhance how we know brain processes task-specific events,? commented Dr. Shyam Diwakar, Director of Computational Neuroscience Lab, Amrita School of Biotechnology in Kerala, India. ?Studies like these may help develop better understanding of memory consolidation and how we understand sleep, learning and other cognitive processes. For pharmacology, this will also help understand neural behaviour in order to develop on better drugs.?
The so-called sharp wave ripples (SWRs) are one of the three major brain waves coming from the hippocampus – the storehouse of emotion, memory and the automatic nervous system. SWRs are one of the most synchronous oscillations in the brain. Their name derives from their characteristic trace when measuring local field potential: the slow sharp waves have a triangular shape with ripples, or fast field oscillations, added on. SWRs have been suggested to play a key role in making memories permanent.
In this study, the researchers wanted to identify whether ripples are caused by a temporal modulation of excitation or of inhibition at the synapse, the connection between neurons. ?SWRs play an important role in the brain, but the mechanism generating them has not been identified so far ? probably partly because of technical limitations in the experiments,? said Professor Jozsef Csicsvari, a collaborator in the research. ?We combined the Jonas group?s experience in recording under voltage-clamp conditions with my group?s expertise in analyzing electrical signals while animals are behaving. This collaborative effort made unprecedented measurements possible and we could achieve the first high resolution recordings of synaptic currents during SWR in behaving mice.?
The neuroscientists found that the frequency of both excitatory and inhibitory events at the synapse increased during SWRs. But quantitatively, synaptic inhibition dominated over excitation during the generation of SWRs. Furthermore, the magnitude of inhibitory events positively correlated with SWR amplitude, indicating that the inhibitory events are the driver of the oscillation. Inhibitory events were phase locked to individual cycles of ripple oscillations. Finally, the researchers showed that so-called PV+ interneurons ? neurons that provide inhibitory output onto other neurons ? are mainly responsible for generating SWRs.
Explaining synaptic inhibition, Dr. Diwakar said Neurons can be excited (stimulated) or inhibited by inputs. Excitation means neurons are facilitating firing or generating signals. Inhibition is preventing a neuron from firing. Synaptic inhibition is crucial to help control movement, anxiety, mood etc. Inhibition failure can show diseases such as epilepsy, sleep disorders, drug and alcohol addiction etc. although it is also seen in chronic pain, fatigue and poor relaxation. Too much fear, anxiety pain are also hypothesized to be from too little inhibition. In cerebellum, per say, inhibitory inputs define time-window or how much information is transmitted which helps predict movement and coordination errors.
