Research reveals 'exquisite selectivity' ofneuronal wiring in the cerebral cortex21 August 2017

The CSHL team traced local and long-range connectionsof chandelier cells in the mouse brain. Arrow heads pointto two of the chandelier cell soma or cell bodies, fromeach of which hundreds of candelabra-like arbors reachout to connect with local pyramidal neurons in a part ofthe cerebral cortex. These spatially intermixed excitatoryneurons segregated into two groups, distinguishedaccording to where in the brain they project to and theirlikely function. The chandelier cell can inhibit one group,causing a fear reaction to stop; from the other group itreceives high-level information from elsewhere in thecortex that presumably informs its inhibitory activity.Credit: Huang Lab, CSHL

The brain's astonishing anatomical complexity hasbeen appreciated for over 100 years, whenpioneers first trained microscopes on the profusionof branching structures that connect individualneurons. Even in the tiniest areas of brain tissue,the pathways are tangled, almost indescribablydense. Today, neuroscientists are trying to figureout the workings of all those cells and the networksthey form, the ultimate grand-challenge problem.

In a study appearing today in NatureNeuroscience, a team from Cold Spring HarborLaboratory (CSHL) uses advanced technologies toilluminate the connectivity pattern of chandelier cells, a distinctive kind of inhibitory cell type in the

mammalian brain. They reveal for the first time howthis candelabra-shaped cell interacts with hundredsof excitatory cells in its neighborhood, receivinginformation from some, imparting information toothers.

In the experiments just reported, these highlyspecific interactions are situated in the context of alarger global network regulating the fear responsein mice. Chandelier cells play analogous roles inother networks, capable of inhibiting excitatory neurons in a variety of contexts. The researchtherefore suggests more broadly howcommunication hierarchies may be shaped in thebrain, as diverse and often intermingled sets ofneurons in "local" areas both receive inputs fromand send outputs to distinct brain areas, near andfar.

The team, led by CSHL Professor Z. Josh Huangand including researcher Joshua Gordon, M.D.,Ph.D., director of the National Institute of MentalHealth, focused on dense crowds of excitatory cellscalled pyramidal neurons - several hundred ofwhich can connect with a single chandelier cell.Because each chandelier cell may control the firingof hundreds of pyramidal neurons, it has beensuggested that they exert a kind of "veto" powerover local excitatory messages. But there is moreto the story. As this research shows, eachchandelier cell also can receive inputs fromhundreds of excitatory cells, input that influenceswhether or not it inhibits a circuit in which it isinvolved.

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The chandelier cell, discovered only 45 years ago, is oneof the most distinctive cells int he mammalian brain. Eachone can synapse with hundreds of neighboring excitatorycells, accounting for its candelabra-like shape. Newresearch is beginning to reveal how they work. Credit:Huang Lab, CSHL

The new research reveals how spatially intermixedpyramidal neurons that were associated with single chandelier cells in the mouse prelimbic cortexsegregated into two groups. These weredistinguished according to where in the brain theyproject to and their likely function.

One ensemble of these pyramidal cells was shownto transmit information to the amygdala, resulting ina fear response; this ensemble can be inhibited bythe chandelier cell. A second ensemble projects tocortical areas conveying information from thethalamus, a relay station that Huang speculates issending higher-order information to the chandeliercell. This information might reflect, for example,whether the individual (whether mouse, person, orother mammal) should be afraid of something that ithas sensed in its environment, given pastexperience.

"This circuit highlights the exquisite selectivity ofneuronal wiring with respect to inhibition in the most

complex and heterogeneous part of the brain,"Huang says. "It also illustrates the directionality ofinformation flow in local and global brain networks.The messages move in a specific direction - thechandelier cell's overall inhibitory and information-routing role being the result of signals to it and fromit by specific sets of neurons to which it isconnected."

This circuit diagram summarizes the findings of Huangand colleagues. A chandelier cell (red) can inhibitexcitatory pyramidal neurons (green) in a fear circuit thatleads to the amygdala (BLA). A separate set of excitatoryneurons (blue) provides input to the chandelier cell, mostdirectly from the thalamus, and possibly reflecting high-order cortical information pertaining to the fear reaction.Credit: Huang Lab, CSHL

More information: Selective inhibitory control ofpyramidal neuron ensembles and corticalsubnetworks by chandelier cells, NatureNeuroscience (2017). DOI: 10.1038/nn.4624

Provided by Cold Spring Harbor Laboratory

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APA citation: Research reveals 'exquisite selectivity' of neuronal wiring in the cerebral cortex (2017,August 21) retrieved 13 February 2022 from https://medicalxpress.com/news/2017-08-reveals-exquisite-neuronal-wiring-cerebral.html

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