One of the brain waves important for consolidating memory is dominated by synaptic inhibition, revealed a new study published in Neuron.
Every time we learn something new, the memory does not only need to
be acquired, it also needs to be stabilized in a process called memory
consolidation. 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 newly identified mechanism that regulates rhythmic brain waves - inhibition at synapses is the key to make memories permanent.’
So-called sharp wave ripples (SWRs) are one of three major brain
waves coming from the hippocampus. The new study, a cooperation between
the research groups of Professors Peter Jonas and Jozsef Csicsvari 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." explains
author Professor Peter Jonas.
When neurons oscillate in synchrony, their electrical activity adds
together so that measurements of field potential can pick them up. 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
For Professor Jozsef Csicsvari, a pooling of expertise was
crucial in answering this question: "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. 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.
The authors propose a model involving two specific regions in the
hippocampus, CA1 and CA3. In their model SWRs are generated by a
combination of tonic excitation from the CA3 region and phasic
inhibition within the CA1 region. Jian Gan, first author and postdoc in
the group of Peter Jonas, explains the implications for temporal coding
of information in the CA1 region: "In our ripple model, inhibition
ensures the precise timing of neuronal firing. This could be critically
important for preplay or replay of neuronal activity sequences, and the
consolidation of memory. Inhibition may be the crucial player to make