Research reveals 'exquisite selectivity' of neuronal wiring in the cerebral cortex

August 21, 2017, Cold Spring Harbor Laboratory
The CSHL team traced local and long-range connections of chandelier cells in the mouse brain. Arrow heads point to two of the chandelier cell soma or cell bodies, from each of which hundreds of candelabra-like arbors reach out to connect with local pyramidal neurons in a part of the cerebral cortex. These spatially intermixed excitatory neurons segregated into two groups, distinguished according to where in the brain they project to and their likely function. The chandelier cell can inhibit one group, causing a fear reaction to stop; from the other group it receives high-level information from elsewhere in the cortex that presumably informs its inhibitory activity. Credit: Huang Lab, CSHL

The brain's astonishing anatomical complexity has been appreciated for over 100 years, when pioneers first trained microscopes on the profusion of branching structures that connect individual neurons. Even in the tiniest areas of brain tissue, the pathways are tangled, almost indescribably dense. Today, neuroscientists are trying to figure out the workings of all those cells and the networks they form, the ultimate grand-challenge problem.

In a study appearing today in Nature Neuroscience, a team from Cold Spring Harbor Laboratory (CSHL) uses advanced technologies to illuminate the connectivity pattern of chandelier , a distinctive kind of inhibitory cell type in the mammalian . They reveal for the first time how this candelabra-shaped cell interacts with hundreds of excitatory cells in its neighborhood, receiving information from some, imparting information to others.

In the experiments just reported, these highly specific interactions are situated in the context of a larger global network regulating the fear response in mice. Chandelier cells play analogous roles in other networks, capable of inhibiting excitatory in a variety of contexts. The research therefore suggests more broadly how communication hierarchies may be shaped in the brain, as diverse and often intermingled sets of neurons in "local" areas both receive inputs from and send outputs to distinct brain areas, near and far.

The team, led by CSHL Professor Z. Josh Huang and including researcher Joshua Gordon, M.D., Ph.D., director of the National Institute of Mental Health, focused on dense crowds of excitatory cells called - several hundred of which can connect with a single chandelier cell. Because each chandelier cell may control the firing of hundreds of pyramidal neurons, it has been suggested that they exert a kind of "veto" power over local excitatory messages. But there is more to the story. As this research shows, each chandelier cell also can receive inputs from hundreds of excitatory cells, input that influences whether or not it inhibits a circuit in which it is involved.

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

The new research reveals how spatially intermixed pyramidal neurons that were associated with single in the mouse prelimbic cortex segregated into two groups. These were distinguished according to where in the brain they project to and their likely function.

One ensemble of these pyramidal cells was shown to transmit information to the amygdala, resulting in a fear response; this ensemble can be inhibited by the chandelier cell. A second ensemble projects to cortical areas conveying information from the thalamus, a relay station that Huang speculates is sending higher-order information to the chandelier cell. This information might reflect, for example, whether the individual (whether mouse, person, or other mammal) should be afraid of something that it has sensed in its environment, given past experience.

"This circuit highlights the exquisite selectivity of neuronal wiring with respect to inhibition in the most complex and heterogeneous part of the brain," Huang says. "It also illustrates the directionality of information flow in local and global brain networks. The messages move in a specific direction - the chandelier cell's overall inhibitory and information-routing role being the result of signals to it and from it by specific sets of neurons to which it is connected."

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

Explore further: New findings reverse hypothesis of GABA neurodevelopment in schizophrenia

More information: Selective inhibitory control of pyramidal neuron ensembles and cortical subnetworks by chandelier cells, Nature Neuroscience (2017). DOI: 10.1038/nn.4624

Related Stories

New findings reverse hypothesis of GABA neurodevelopment in schizophrenia

June 20, 2017
New research by scientists at the University of Pittsburgh provides an unprecedented level of resolution and insight into disturbances in cortical GABAergic microcircuits, which are thought to underlie cognitive impairments ...

Distinct wiring mode found in chandelier cells

June 9, 2017
A basic tenet of neural development is that young neurons make far more connections than they will actually use, with very little specificity. They selectively maintain only the ones that they end up needing. Once many of ...

Scientists discover two proteins that control chandelier cell architecture

January 16, 2014
Chandelier cells are neurons that use their unique shape to act like master circuit breakers in the brain's cerebral cortex. These cells have dozens, often hundreds, of branching axonal projections – output channels from ...

Study solves birth and migration mysteries of cortex's powerful inhibitors, 'chandelier' cells

November 22, 2012
A team at CSHL for the 1st time reveals the birth timing and embryonic origin of a critical class of inhibitory brain cells called chandelier cells, tracing the specific paths they take during early development into the cerebral ...

New insights into how inhibitory neurons contribute to functional networks in the cortex

March 8, 2017
It takes a village—of neurons—that is, to process sensory inputs in the brain. For example, when a line appears in our visual field, networks of neurons fire together and send messages throughout the brain to identify ...

Recommended for you

Wiring diagram of the brain provides a clearer picture of brain scan data

December 14, 2018
Already affecting more than five million Americans older than 65, Alzheimer's disease is on the rise and expected to impact more than 13 million people by 2050. Over the last three decades, researchers have relied on neuroimaging—brain ...

Scientists identify method to study resilience to pain

December 14, 2018
Scientists at the Yale School of Medicine and Veterans Affairs Connecticut Healthcare System have successfully demonstrated that it is possible to pinpoint genes that contribute to inter-individual differences in pain.

Parents' brain activity 'echoes' their infant's brain activity when they play together

December 13, 2018
When infants are playing with objects, their early attempts to pay attention to things are accompanied by bursts of high-frequency activity in their brain. But what happens when parents play together with them? New research, ...

In the developing brain, scientists find roots of neuropsychiatric diseases

December 13, 2018
The most comprehensive genomic analysis of the human brain ever undertaken has revealed new insights into the changes it undergoes through development, how it varies among individuals, and the roots of neuropsychiatric illnesses ...

Researchers find the cause of and cure for brain injury associated with gut condition

December 13, 2018
Using a mouse model of necrotizing enterocolitis (NEC)—a potentially fatal condition that causes a premature infant's gut to suddenly die—researchers at Johns Hopkins say they have uncovered the molecular causes of the ...

Researchers discover abundant source for neuronal cells

December 13, 2018
USC researchers seeking a way to study genetic activity associated with psychiatric disorders have discovered an abundant source of human cells—the nose.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.