Neural “Synchrony” May be Key to Understanding How the Human Brain Perceives

Despite many remarkable discoveries in the field of neuroscience during the past several decades, researchers have not been able to fully crack the brain’s “neural code.” The neural code details how the brain’s roughly 100 billion neurons turn raw sensory inputs into information we can use to see, hear and feel things in our environment.

In a perspective article published in the journal Nature Neuroscience on Feb. 25, 2013, biomedical engineering professor Garrett Stanley detailed research progress toward “reading and writing the neural code.” This encompasses the ability to observe the spiking activity of neurons in response to outside stimuli and make clear predictions about what is being seen, heard, or felt, and the ability to artificially introduce activity within the brain that enables someone to see, hear, or feel something that is not experienced naturally through sensory organs.

Stanley also described challenges that remain to read and write the neural code and asserted that the specific timing of electrical pulses is crucial to interpreting the code. He wrote the article with support from the National Science Foundation (NSF) and the National Institutes of Health (NIH). Stanley has been developing approaches to better understand and control the neural code since 1997 and has published about 40 journal articles in this area.

“Neuroscientists have made great progress toward reading the neural code since the 1990s, but the recent development of improved tools for measuring and activating neuronal circuits has finally put us in a position to start writing the neural code and controlling neuronal circuits in a physiological and meaningful way,” said Stanley, a professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.

With recent reports that the Obama administration is planning a decade-long scientific effort to examine the workings of the human brain and build a comprehensive map of its activity, progress toward breaking the neural code could begin to accelerate.

The potential rewards for cracking the neural code are immense. In addition to understanding how brains generate and manage information, neuroscientists may be able to control neurons in individuals with epilepsy and Parkinson’s disease or restore lost function following a brain injury. Researchers may also be able to supply artificial brain signals that provide tactile sensation to amputees wearing a prosthetic device.

Stanley’s paper highlighted a major challenge neuroscientists face: selecting a viable code for conveying information through neural pathways. A longstanding debate exists in the neuroscience community over whether the neural code is a “rate code,” where neurons simply spike faster than their background spiking rate when they are coding for something, or a “timing code,” where the pattern of the spikes matters. Stanley expanded the debate by suggesting the neural code is a “synchrony code,” where the synchronization of spiking across neurons is important.

A synchrony code argues the need for precise millisecond timing coordination across groups of neighboring neurons to truly control the circuit. When a neuron receives an incoming stimulus, an electric pulse travels the neuron’s length and triggers the cell to dump neurotransmitters that can spark a new impulse in a neighboring neuron. In this way, the signal gets passed around the brain and then the body, enabling individuals to see, touch, and hear things in the environment. Depending on the signals it receives, a neuron can spike with hundreds of these impulses every second.

“Eavesdropping on neurons in the brain is like listening to a bunch of people talk—a lot of the noise is just filler, but you still have to determine what the important messages are,” explained Stanley. “My perspective is that information is relevant only if it is going to propagate downstream, a process that requires the synchronization of neurons.”

Neuronal synchrony is naturally modulated by the brain. In a study published in Nature Neuroscience in 2010, Stanley reported finding that a change in the degree of synchronous firing of neurons in the thalamus altered the nature of information as it traveled through the pathway and enhanced the brain’s ability to discriminate between different sensations. The thalamus serves as a relay station between the outside world and the brain’s cortex.

Synchrony induced through artificial stimulation poses a real challenge for creating a wide range of neural representations. Recent technological advances have provided researchers with new methods of activating and silencing neurons via artificial means. Electrical microstimulation had been used for decades to activate neurons, but the technique activated a large volume of neurons at a time and could not be used to silence them or separately activate excitatory and inhibitory neurons. Stanley compared the technique with driving a car that has the gas and brake pedals welded together.

New research methods, such as optogenetics, enable activation and silencing of neurons in close proximity and provide control unavailable with electrical microstimulation. Through genetic expression or viral transfection, different cell types can be targeted to express specific proteins that can be activated with light.

“Moving forward, new technologies need to be used to stimulate neural activity in more realistic and natural scenarios and their effects on the synchronization of neurons need to be thoroughly examined,” said Stanley. “Further work also needs to be completed to determine whether synchrony is crucial in different contexts and across brain regions.”

Star-Shaped Glial Cells Act as the Brain’s “Motherboard”

The transistors and wires that power our electronic devices need to be mounted on a base material known as a “motherboard.” Our human brain is not so different — neurons, the cells that transmit electrical and chemical signals, are connected to one another through synapses, similar to transistors and wires, and they need a base material too.

But the cells serving that function in the brain may have other functions as well. PhD student Maurizio De Pittà of Tel Aviv University’s Schools of Physics and Astronomy and Electrical Engineering says that astrocytes, the star-shaped glial cells that are predominant in the brain, not only control the flow of information between neurons but also connect different neuronal circuits in various regions of the brain.

Using models designed to mimic brain signalling, De Pittà’s research, led by his TAU supervisor Prof. Eshel Ben-Jacob, determined that astrocytes are actually “smart” in addition to practical. They integrate all the different messages being transferred through the neurons and multiplexing them to the brain’s circuitry. Published in the journal Frontiers in Computational Neuroscience and sponsored by the Italy-Israel Joint Neuroscience Lab, this research introduces a new framework for making sense of brain communications — aiding our understanding of the diseases and disorders that impact the brain.

Transcending boundaries

"Many pathologies are related to malfunctions in brain connectivity," explains Prof. Ben-Jacob, citing epilepsy as one example. "Diagnosis and the development of therapies rely on understanding the network of the brain and the source of undesirable activity."

Connectivity in the brain has traditionally been defined as point-to-point connections between neurons, facilitated by synapses. Astrocytes serve a protective function by encasing neurons and forming borders between different areas of the brain. These cells also transfer information more slowly, says Prof. Ben-Jacob — one-tenth of a second compared to one-thousandth of a second in neurons — producing signals that carry larger amounts of information over longer distances. Aastrocytes can transfer information regionally or spread it to different areas throughout the brain — connecting neurons in a different manner than conventional synapses.

De Pittà and his fellow researchers developed computational models to look at the different aspects of brain signalling, such as neural network electrical activity and signal transfer by synapses. In the course of their research, they discovered that astrocytes actually take an active role in the way these signals are distributed, confirming theories put forth by leading experimental scientists.

Astrocytes form additional networks to those of the neurons and synapses, operating simultaneously to co-ordinate information from different regions of the brain — much like an electrical motherboard functions in a computer, or a conductor ensuring that the entire orchestra is working in harmony, explains De Pittà.

These findings should encourage neuroscientists to think beyond neuron-based networks and adopt a more holistic view of the brain, he suggests, noting that the two communication systems are actually interconnected, and the breakdown of one can certainly impact the other. And what may seem like damage in one small area could actually be carried to larger regions.

A break in communication

According to Prof. Ben-Jacob, a full understanding of the way the brain sends messages is significant beyond satisfying pure scientific curiosity. Many diseases and disorders are caused by an irregularity in the brain’s communication system or by damage to the glial cells, so more precise information on how the network functions can help scientists identify the cause or location of a breakdown and develop treatments to overcome the damage.

In the case of epilepsy, for example, the networks frequently become overexcited. Alzheimer’s disease and other memory disorders are characterized by a loss of cell-to-cell connection. Further understanding brain connectivity can greatly aid research into these and other brain-based pathologies.

Hypothalamic control of energy balance: insights into the role of synaptic plasticity

The past 20 years witnessed an enormous leap in understanding of the central regulation of whole-body energy metabolism. Genetic tools have enabled identification of the region-specific expression of peripheral metabolic hormone receptors and have identified neuronal circuits that mediate the action of these hormones on behavior and peripheral tissue functions. One of the surprising findings of recent years is the observation that brain circuits involved in metabolism regulation remain plastic through adulthood. In this review, we discuss these findings and focus on the role of neurons and glial cells in the dynamic process of plasticity, which is fundamental to the regulation of physiological and pathological metabolic events.

Purkinje neurons (yellow) generated from embryonic stem cells integrate into the cerebellum (red) when transplanted into the fetal mouse brain.

© 2010 K. Muguruma et al.