When we learn, we associate a sensory experience either with other stimuli or with a certain type of behaviour. The neurons in the cerebral cortex that transmit the information modify the synaptic connections that they have with the other neurons. According to a generally accepted model of synaptic plasticity, a neuron that communicates with other neurons emits an electrical impulse, which thereby transiently activates its own synapses. This electrical impulse, combined with the signals received from other neurons, acts to strengthen the synapses. However, this model assumes that neurons bear strong enough connections to make them send electrical pulses. How then are synapses strengthened if neurons are barely connected and therefore do not send electrical impulses? This is the crucial chicken-or-egg puzzle of synaptic plasticity that a team led by Anthony Holtmaat, professor in the Department of Basic Neurosciences in the Faculty of Medicine at UNIGE, aimed to solve. The results of their research on this memory of silent neurons can be found in the latest edition of Nature.
Learning and memory are governed by a mechanism of sustained synaptic strengthening. When we embark on a learning experience, our brain associates a sensory experience either with other stimuli or with a certain form of behaviour. The neurons in the cerebral cortex responsible for ensuring the transmission of the relevant information then modify the synaptic connections that they have with other neurons. It is this arrangement that subsequently enables the brain to optimise the way information is processed when it is experienced again, as well as to predict its consequences.
Typically, to study synaptic plasticity neuroscientists artificially induce electrical pulses in neurons in order to transiently activate synapses. The neuroscientists from UNIGE, however, chose a different approach and attempted to discover what happens in neurons when these only receive sensory stimuli. They measured synaptic plasticity in neurons in the cerebral cortex of mice while their whiskers were repeatedly stimulated mechanically, without artificially inducing electrical pulses in the neurons. The rodents use their whiskers as a sensor for navigating and interacting; they are, therefore, key for perception in mice.
An Extremely Low Signal is Enough
By observing these natural stimuli, professor Holtmaat’s team was able to demonstrate that the sensory stimulus alone can generate long-term synaptic strengthening without the neuron discharging either an induced or natural electrical pulse. As a result – and contrary to what was previously believed – the synapses were strengthened, even when the neurons remained silent.
This means that if the sensory stimulation lasts for some time, the synapses may become stronger and stronger until a point that the neuron starts sending electrical impulses and thus becomes fully engaged in the neural network. Once activated, the neuron can then further strengthen the synapses due to the generation of electrical impulses induced by whisker movements.These findings could solve the brain’s “What comes first?” mystery, and now allows them to focus on the question which synaptic pathways activate those synapses and thereby contribute to memory, rather than on finding out which stimuli are strong enough to activate the whole neuron.
The Entire Brain is Mobilised
A second discovery lay in store for the researchers. During the same experiment, they were also able to establish that the stimuli that were most effective in strengthening the synapses came from secondary, non-cortical brain regions rather than from the major cortical pathways (which convey actual sensory information). Accordingly, storing information would simply require the co-activation of several synaptic pathways of the neuron, even if the latter remains silent. These findings may also have important implications both for understanding the way we learn and for therapeutic possibilities, in particular for rehabilitation following a stroke or in neurodegenerative disorders. As professor Holtmaat explains: “It is possible that sensory stimulation, when combined with other activity (motor activity, for example), works better for strengthening synaptic connections”. The professor concludes: “In the context of therapy, you could combine two different stimuli as a way of enhancing its effectiveness.”
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