As a brain grows, the neurons within it establish themselves, forming lasting connections with their neighbors. Now, researchers have determined how a crucial kind of mammalian neuron called a chandelier cell forms connections with other neurons, opening new avenues for understanding mental illness.
Compared with other kinds of neurons in the mammalian brain, chandelier cells are sparse in number. But they make up for their lower density by reaching a long way with drooping fibers that make them look like their namesake. It’s the endings of these reaching fibers, called cartridges, that allow chandelier cells to connect with many neighboring excitatory pyramidal neurons. Chandelier cells connect with pyramidal neurons at one particular anatomical location: the axon initial segment—a spot where a spiking pyramidal neuron generates its transmittable message.
So how does the chandelier cell make lasting connections? In a study published today in Neuron, a team of researchers from Cold Spring Harbor Laboratory show that the presence of one specific molecule was the key to determining whether a chandelier cell’s arbor would connect with any pyramidal neuron.
“Imagine these connections as something like Velcro. On one cell you have little hooks. On the other, you have felt. They latch together,” says co–first author Nicholas Gallo. “In our situation, we found this molecule called L1CAM is the ‘hooks.’” L1CAM can be found on the surface of pyramidal neurons, where it forms synapses by latching onto the chandelier cell.
The researchers tested 14 molecules that might mediate this connection, but only L1CAM seemed to be essential. Without it, a pyramidal neuron is ignored by a chandelier cell during “establishment,” or the initial forming of a connection. Further, the molecule is required not just for the initial connection but also for maintaining established connections.
“If you get rid of L1CAM after all synapses have been formed, you still see an impact on the contact point,” says senior author Linda Van Aelst. “It falls apart.”
Poor connectivity of chandelier cells has been linked to neurological conditions like schizophrenia and epilepsy. Now, the researchers hope to identify the “felt” side of this molecular Velcro, potentially leading to new avenues for neurological drug discovery.
Image: The long, reaching fibers—called cartridges—of a single chandelier cell (ChC) can be seen highlighted in red in this image. Each fiber forms a lasting connection with a neighboring pyramidal neuron (PyN) (green). This partnership ensures that the PyNs don’t become overexcited, a state which can result in problems like epilepsy and even neuron death. The anchor protein AnkG (blue) helps hold an essential molecule (see inline image) to the axon initial segment of the PyN, which in turn maintains the crucial connection with the ChC cartridge. Image courtesy of CSHL/Van Aelst.