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Brain cells shout in unison to get a message through

April 1, 2010
Courtesy Salk Institute
and World Science staff

There is strength in num­bers if you want to get your voice heard. But how do you get your say if you are in the mi­nor­ity? That's a di­lem­ma faced not only by the cit­i­zens of a de­moc­ra­cy but al­so by some brain cells.

Neu­rons, or in­forma­t­ion-pas­sing brain cells, in a key brain struc­ture called the thal­a­mus ac­count for just a frac­tion of the con­nec­tions among cells in the brain's ad­vanced vis­u­al pro­cess­ing ar­eas, sci­en­tists say. 

Though they on­ly ac­count for a frac­tion of the synapses in the vis­u­al cor­tex, neu­rons in the thal­a­mus (shown in red) get their mes­sage across by si­mul­ta­ne­ous­ly hit­ting the "send" but­ton, re­search­ers say. (Cred­it: From An­a­to­mog­ra­phy, web­site main­tained by Life Sci­ence Data­bases)


But the cells in the thala­mus get their mes­sages across loud and clear by co­ord­in­a­t­ion -- sim­ul­ta­ne­ously hit­ting the "send" but­ton, say re­search­ers at the Salk In­sti­tute for Bi­o­log­i­cal Stud­ies in La Jolla, Ca­lif.

Their find­ings, based on com­put­er sim­ula­t­ions and pub­lished in the April 2 is­sue of the re­search jour­nal Sci­ence, hold im­por­tant clues to how the brain en­codes and pro­cesses in­forma­t­ion, they say.

His­tor­ic­ally, neu­ro­sci­en­tists have been lim­it­ed to re­cord­ing the ac­ti­vity of sin­gle brain cells. This led to the con­ven­tion­al un­der­stand­ing that neu­rons com­mu­ni­cate with each oth­er through vol­leys of elec­tri­cal spikes and that they in­crease the av­er­age rate of spik­ing to "s­peak up."

But com­mu­nica­t­ion be­tween neu­rons is­n’t lim­it­ed to one-on-one in­ter­ac­tions. In­stead, any giv­en cell re­ceives sig­nals from hun­dreds of cells, which send their mes­sages through thou­sands of synapses, spe­cial­ized junc­tions that al­low sig­nals to pass from one neu­ron to the next.

"Un­for­tu­nately, we don't have the tech­nol­o­gy yet to ac­tu­ally meas­ure what all these neu­rons are say­ing to the re­cip­i­ent cell, which would re­quire re­cord­ing sim­ul­ta­ne­ously from hun­dreds of cells," said grad­u­ate stu­dent Hsi-Ping Wang, an au­thor of the stu­dy. There­fore, "no­body could an­swer a very bas­ic ques­tion… how many neu­rons or synapses does it take to re­liably send a sig­nal from point A to point B?”

This ques­tion is par­tic­u­larly press­ing for the thal­a­mus, the cen­tral switch­board that pro­cesses and dis­tributes in­com­ing sen­so­ry in­forma­t­ion to all parts of the cor­tex, the ar­ea of the brain con­sid­ered re­spon­si­ble for ad­vanced think­ing and cog­ni­tive func­tions. In­put from the thal­a­mus only ac­counts for five per­cent of the sig­nals that so-called spiny stel­late cells in the cor­tex re­ceive, even though they drive a good por­tion of ac­ti­vity through­out the cor­tex.

"That is a para­dox," said in­ves­ti­ga­tor Ter­rence J. Se­jnowski, head of the in­sti­tute’s Com­puta­t­ional Neuro­bi­ol­o­gy Lab­o­r­a­to­ry. "How can so few synapses have such a big im­pact? If the av­er­age spik­ing rate were the de­ter­min­ing fac­tor, tha­la­mic in­put would be drowned out by the oth­er 95 per­cent of the in­puts."

Based on the as­sump­tion that the brain cares about the re­liabil­ity and pre­ci­sion of spikes, Se­jnowk­i's team de­vel­oped a com­put­er mod­el of a spiny stel­late cell and the sig­nals it re­ceives through its roughly 6,000 synapses. "We found that it is not the num­ber of spikes that's rel­e­vant but rath­er how many spikes ar­rive at the same time," said Se­j­nowski.

"Sur­pris­ingly, our mod­el pre­dicts that it only takes about 30 synapses out of 6,000 fir­ing sim­ul­ta­ne­ously to cre­ate ex­tremely re­liable sig­naling," ex­plains Wang, "and our pre­dic­tion lines up with cur­rently avail­able” meas­urements in liv­ing or­gan­isms. “You could have all 6,000 synapses fir­ing at the same time, but it would be a waste of re­sources."

The re­search­ers hope that their find­ings will give them new in­sight in­to the holy grail of neuro­bi­ol­o­gy: de­cod­ing the neu­ral code, or the lan­guage of the brain. If the eye re­ceives the same vis­u­al in­forma­t­ion un­der iden­ti­cal con­di­tions over and over again, one would ex­pect that the sig­nal, the se­ries of gen­er­at­ed spikes or bits, is es­sen­tially the same.

"But it's not known wheth­er that hap­pens un­der nat­u­ral con­di­tions, and it's tech­nic­ally very dif­fi­cult to meas­ure," said sen­ior re­searcher and co-au­thor Don­ald Spen­cer. "That's where the pow­er of com­puta­t­ional neuro­bi­ol­o­gy really comes to bear on oth­erwise in­trac­ta­ble ques­tions."

"Ap­ply­ing the­o­ries of en­gi­neer­ing to the study of the brain has helped us gain new in­sight in­to how neu­rons com­mu­ni­cate with each oth­er," says Wang. "On the oth­er hand, there are cer­tain things that the brain does in un­ique ways that are com­pletely dif­fer­ent from how com­put­ers work."


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There is strength in numbers if you want to get your voice heard. But how to do you get your say if you are in the minority? That's a dilemma faced not only by the citizens of a democracy but also by some brain cells. Neurons, or information-passing brain cells, in a key brain structure called the thalamus account for a just fraction of the connections among brain cells in the advanced visual processing areas of the brain, scientists say. But these neurons get their message across loud and clear by coordination -- simultaneously hitting the "send" button—according to a computer simulation developed by researchers at the Salk Institute for Biological Studies in La Jolla, Calif. Their findings, published in the April 2 issue of the research journal Science, hold important clues to how the brain encodes and processes information, according to investigators. Historically, neuroscientists have been limited to recording the activity of single brain cells. This led to the conventional understanding that neurons communicate with each other through volleys of electrical spikes and that they increase the average rate of spiking to "speak up." But communication between neurons isn’t limited to one-on-one interactions. Instead, any given cell receives signals from hundreds of cells, which send their messages through thousands of synapses, specialized junctions that allow signals to pass from one neuron to the next. "Unfortunately, we don't have the technology yet to actually measure what all these neurons are saying to the recipient cell, which would require recording simultaneously from hundreds of cells," said graduate student Hsi-Ping Wang, an author of the study. Therefore, "nobody could answer a very basic question… how many neurons or synapses does it take to reliably send a signal from point A to point B?” This question is particularly pressing for the thalamus, the central switchboard that processes and distributes incoming sensory information to all parts of the cortex, the area of the brain considered responsible for advanced thinking and cognitive functions. Input from the thalamus only accounts for five percent of the signals that so-called spiny stellate cells in the cortex receive, even though they drive a good portion of activity throughout the cerebral cortex. "That is a paradox," says investigator Terrence J. Sejnowski, head of the institute’s Computational Neurobiology Laboratory. "How can so few synapses have such a big impact? If the average spiking rate were the determining factor, thalamic input would be drowned out by the other 95 percent of the inputs from other cortical cells." Based on the assumption that the brain cares about the reliability and precision of spikes, Sejnowki's team developed a realistic computer model of a spiny stellate cell and the signals it receives through its roughly 6,000 synapses. "We found that it is not the number of spikes that's relevant but rather how many spikes arrive at the same time," says Sejnowski. "Surprisingly, our model predicts that it only takes about 30 synapses out of 6,000 firing simultaneously to create extremely reliable signaling," explains Wang, "and our prediction lines up with currently available” measurements in living organisms. “You could have all 6,000 synapses firing at the same time, but it would be a waste of resources." The researchers hope that their findings will give them new insight into the holy grail of neurobiology: decoding the neural code or language of the brain. If the eye receives the same visual information under identical conditions over and over again, one would expect that the signal, the series of generated spikes or bits, is essentially the same. "But it's not known whether that happens under natural conditions, and it's technically very difficult to measure, " says senior researcher and co-author Donald Spencer. "That's where the power of computational neurobiology really comes to bear on otherwise intractable questions." "Applying theories of engineering to the study of the brain has helped us gain new insight into how neurons communicate with each other," says Wang. "On the other hand, there are certain things that the brain does in unique ways that are completely different from how computers work. A better understanding of the brain allows us the capture these algorithms and could very well affect the things engineers do in everyday life."