Scientists at Ecole Polytechnique Fédérale de Lausanne (EPFL) have revealed a mechanism responsible for the creation of giant synapses in the brain that allow us to efficiently process auditory information.

Humans and most mammals can determine the spatial origin of sounds with remarkable acuity. We use this ability when we cross the street or locate an invisible ringing cell phone in a cluttered bedroom. To accomplish this task, the brain has developed a circuit that’s rapid enough to detect the tiny lag that occurs between the moment the auditory information reaches one of our ears, and the moment it reaches the other. The mastermind of this circuit is the “Calyx of Held,” the largest known synapse in the brain.

EPFL scientists have revealed the role that a certain protein plays in initiating the growth of these giant synapses. The discovery, published in Nature Neuroscience, could also help shed light on a number of neuropsychiatric disorders.

In the auditory part of the brain, synapses often grow to extremely large sizes, and these behemoths are known as “Calyx of Held” synapses. Because they have hundreds of contact points, they are capable of transmitting a signal singlehandedly to a neighboring neuron. “It’s almost like one-to-one communication between neurons,” explains EPFL professor Ralf Schneggenburger, who led the study. The result is that information is processed extremely quickly, in a few fractions of a millisecond, instead of the slower pace of more than 10 milliseconds that occurs in most other neuronal circuits.

To isolate the protein responsible for controlling the growth of this gigantic synapse, the scientists used methods for analyzing gene expression in mice and identified several members of the “BMP” family of proteins from among more than 20,000 possible candidates.

To verify that they had truly identified the right protein, the researchers disabled BMP protein receptors in the auditory part of a mouse brain. “The resulting electrophysiological signal of the Calyx of Held was significantly altered,” explains Le Xiao, first author on the study. “This would suggest a large anatomical difference.”

EFPL Synapse Auditory
In green, a normal Calyx of Held synapse covering the neuron soma in a mouse brain. On right, researchers disabled BMP protein receptors in the auditory part of a mouse brain. The resulting electrophysiological signal of the Calyx of Held was significantly altered. Instead of a single, massive Calyx of Held, the neuron shows several smaller synapses. © EPFL/Schneggenburger

The scientists then reconstructed the synapses in three dimensions from slices that were observed under an electron microscope. Instead of a single, massive Calyx of Held, which would encompass nearly half the neuron, the 3D image of the neuron clearly shows several, smaller synapses. “This shows that the process involving the BMP protein not only causes that one synapse to grow, but also performs a selection, by eliminating the others,” says Schneggenburger.

The impact of this study will go well beyond increasing our understanding of the auditory system. The results suggest that the BMP protein plays an important role in developing connectivity in the brain.

Schneggenburger and his colleagues are currently investigating its role in neuropsychiatric disorders, such as schizophrenia and autism, which are characterized by the abnormal development of synaptic connectivity in certain key parts of the brain.

SOURCE: Ecole Polytechnique Fédérale de Lausanne (EPFL)