Neurons that fire together, don't always wire together

November 8, 2018, Sainsbury Wellcome Centre
Primary visual cortex neurons projecting to higher visual area AL. Credit: Sainsbury Wellcome Centre

As the adage goes "neurons that fire together, wire together," but a new paper published today in Neuron demonstrates that, in addition to response similarity, projection target also constrains local connectivity.

Researchers from the Sainsbury Wellcome Centre have been looking to elucidate the rules of connectivity of neurons in the neocortex with the long term goal of building models to understand how the brain makes computations and how properties of neurons arise from the structure of their connections.

Traditionally, neurons that project within the cortex have been thought to be homogeneous, particularly in comparison to neurons that project from the cortex to other areas of the brain, but it is becoming clear that these cortical-cortical cells are actually quite diverse.

In the study, Kim, Znamenskiy et al. examined the connections between different types of excitatory neurons in the primary visual cortex (V1) that project to two higher visual areas, anterolateral (AL) and posteromedial (PM), in mice.

Building on previous research, the study found biases between the cell populations: one population preferred fast moving, coarser visual stimuli and the other population preferred slow moving, finer-scale visual stimuli. But many neurons in both populations shared their preference for visual stimuli.

Importantly, the researchers found that cells with the same projection target (e.g. the AL-projecting neurons) made connections with one another but rarely made connections with their PM-projecting neighbours. "Cells projecting to different targets are excluded from interacting with each other, despite being neighbours. This is new 'exclusion' principle of connectivity is puzzling given that these neurons frequently respond together to the same sensory stimuli", says Tom Mrsic-Flogel, a senior author on the study.

Why might it be that there is very little cross-talk between these two output channels within visual cortex? Previous work from the Mrsic-Flogel lab showed that you can predict which cells in connect by looking at their responses. Cells that are active at the same time and respond to similar types of are much more likely to connect to each other. However, this does not hold for AL- and PM-projecting which are functionally quite similar but somehow avoid making connections with one another. One possibility is that the signals transmitted by these cell populations are kept separate to allow independent control of these output pathways.

If they fire together but are not wiring together, how are these parallel channels to AL and PM are set up? One future avenue is to explore whether there are molecular mechanisms that dictate these specific wiring rules. The researchers will also explore how widespread these 'hardwired' patterns of connectivity are in the brain.

Petr Znamenskiy, joint first author on the paper, commented on the importance of the work: "The flow of information in the brain is defined by where get their inputs and where they send their outputs. To gain a mechanistic understanding of neural computations, we need to know these rules of connections."

Future research will focus on the functions of these independent output channels and how individual decide what inputs to select and where to send their axons. Through further understanding of the molecular mechanisms of these rules, the researchers hope to piece together the processes that govern the brain's intricate wiring.

Explore further: Brain-wide tracing of single neurons reveals breadth of information transfer from visual cortex

More information: Mean-Hwan Kim et al, Segregated Subnetworks of Intracortical Projection Neurons in Primary Visual Cortex, Neuron (2018). DOI: 10.1016/j.neuron.2018.10.023

Related Stories

Brain-wide tracing of single neurons reveals breadth of information transfer from visual cortex

March 28, 2018
An international collaboration of neuroscientists have today published a paper in Nature demonstrating the breadth of neural communication in visual cortex using a combination of methods for tracing the projections of individual ...

Neural connections mapped with unprecedented detail

July 4, 2016
A team of neuroscientists at the Champalimaud Centre for the Unknown, in Lisbon, has been able to map single neural connections over long distances in the brain. "These are the first measurements of neural inputs between ...

Surprising network activity in the immature brain

October 26, 2018
One of the outstanding mysteries of the cerebral cortex is how individual neurons develop the proper synaptic connections to form large-scale, distributed networks. Now, an international team of scientists including researchers ...

Neurons reliably respond to straight lines

October 23, 2018
Single neurons in the brain's primary visual cortex can reliably detect straight lines, even though the cellular makeup of the neurons is constantly changing, according to a new study by Carnegie Mellon University neuroscientists, ...

Revolutionary brain-mapping technique provides new blueprint for cortical connections

March 28, 2018
Using a revolutionary new brain-mapping technology recently developed at Cold Spring Harbor Laboratory (CSHL), an international team of scientists led by Professor Anthony Zador have made a discovery that will force neuroscientists ...

Unconventional connections: How inhibition hones cortical selectivity

July 25, 2018
Our brains do a remarkable job of encoding visual information about the world around us, providing an almost instantaneous report about rapidly changing conditions that is critical for guiding our behavior. Integral to the ...

Recommended for you

Scientists identify novel target for neuron regeneration and functional recovery in spinal cord injury

November 19, 2018
Restoring the ability to walk following spinal cord injury requires neurons in the brain to reestablish communication pathways with neurons in the spinal cord. Mature neurons, however, are unable to regenerate their axons ...

How the brain switches between different sets of rules

November 19, 2018
Cognitive flexibility—the brain's ability to switch between different rules or action plans depending on the context—is key to many of our everyday activities. For example, imagine you're driving on a highway at 65 miles ...

Mutation that causes autism and intellectual disability makes brain less flexible

November 19, 2018
About 1 percent of patients diagnosed with autism spectrum disorder and intellectual disability have a mutation in a gene called SETD5. Scientists have now discovered what happens on a molecular level when the gene is mutated ...

Signal peptides' novel role in glutamate receptor trafficking and neural synaptic activity

November 19, 2018
Glutamate is the major excitatory neurotransmitter in the brain, and the postsynaptic expression level of glutamate receptors is a critical factor in determining the efficiency of information transmission and the activity ...

MDMA makes people cooperative, but not gullible

November 19, 2018
New research from King's College London has found that MDMA, the main ingredient in ecstasy, causes people to cooperate better—but only with trustworthy people. In the first study to look in detail at how MDMA impacts cooperative ...

Study explains behavioral reaction to painful experiences

November 19, 2018
Exposure to uncomfortable sensations elicits a wide range of appropriate and quick reactions, from reflexive withdrawal to more complex feelings and behaviors. To better understand the body's innate response to harmful activity, ...

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.