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Molecules May “anchor” Memories In The Brain

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Molecules may “anchor” memories in the brain


Nov. 21, 2006

Courtesy University of Utah

and World Science staff


Our brains nail down mem­o­ries by us­ing spe­cial pro­tein mo­le­cules as an­chors that streng­th­en nerve cell con­nec­tions, a study sug­gests.


These con­nec­tions, called sy­n­apses, “are in a con­s­tant state of flux. They are ex­chang­ing mo­le­cules all the time,” said Paul Bress­loff of the Uni­ver­si­ty of Utah in Salt Lake City.




Deep in­side the brain, a neu­ron pre­pares to trans­mit a sig­nal to its tar­get. This im­age won the U.S. Na­tion­al Sci­ence Foun­d­a­tion's Sci­ence & En­gi­neer­ing Vis­u­al­i­za­tion Chal­lenge im­age com­pe­ti­tion last year. (Cred­it: Gra­ham John­son Med­i­cal Me­dia).




“So how can they be the seat of mem­o­ries that can last a life­time? Part of the an­s­wer is that there are an­chors in­side the sy­n­apse.” These hold in place other pro­teins that de­ter­mine the strength of con­nec­tions, he ar­g­ued, which in turn help form and re­tain mem­o­ries.


The re­search, he said, is also rel­e­vant to learn­ing and Alz­hei­mer’s dis­ease. That ill­ness is thought to in­volve, at least in part, a mal­func­tion in pro­tein move­ments in syn­apses.


Bresloff and a co-author de­tailed their work in the Nov. 22 is­sue of The Jour­nal of Neu­ro­science. Both au­th­ors are math­e­mati­cians, not bi­ol­o­gists. But Bressloff said he’s not wor­ried about pos­si­ble skep­ti­cism from sci­en­tists who may ar­gue that it will take ex­per­i­ments, not math­e­mat­i­cal the­o­ries, to prove his point.


“The­ory can be a real­i­ty check [on] ex­per­i­ments just as much as the oth­er way around,” wrote Bress­loff, a mem­ber of the uni­ver­si­ty’s Brain In­s­ti­tute, in an e­mail.


On the sub­ject that his stu­dy co­vers, he added, there’s al­ready “an over­whelm­ing amount of ex­per­i­men­tal da­ta, much of which ap­pears to be con­tra­dic­to­ry.”


Bressloff said the big de­bate on con­scious­ness is, “can it be ex­plained simp­ly in terms of a bunch of nerve im­pulses in the brain? In my opin­ion, the an­swer has to be yes”—and his find­ings re­in­force that. “If you change the pat­tern of nerve im­pulses, then that changes the mem­o­ries, be­hav­ior and feel­ings. … What de­ter­mines that pat­tern of nerve im­pulses is a mix­ture of stim­u­li we are re­ceiv­ing from the out­side world and the strength of con­nec­tions be­tween nerve cells.”


The strength of these links de­ter­mines who we are, he ar­g­ued.


A syn­apse, the junc­tion be­tween nerve cells or neu­rons, has three parts: an end or “ax­on” of the trans­mit­ting cell; a mi­cro­scop­ic gap be­tween cells; and a mush­room-shaped “den­dritic spine,” which is part of the re­ceiv­ing cell.


What we learn and re­mem­ber is be­lieved to be dis­trib­ut­ed across many syn­apses, Bress­loff said. Some mem­o­ries, such as a per­son’s face, may rely on just a few syn­apses; oth­er mem­o­ries may be dis­trib­ut­ed across many.


While a nerve cell has on­ly one ax­on to trans­mit out­go­ing sig­nals, it has many branch-like struc­tures called den­dri­tes. Each den­drite, in turn, branches in­to twig-like pro­tru­sions known as den­d­rit­ic spines. A nerve cell may have 10,000 den­drit­ic spines, each of which is part of a syn­apse. So the cell can get sig­nals from that many oth­er nerve cells.


Nerve cells fire elec­tric im­pulses. When an im­pulse ar­rives at the syn­apse, it trig­gers the re­lease of chem­i­cals called neurotrans­mitters. These cross the syn­apse and at­tach or “bind” to pro­teins on the den­drit­ic spine, called re­cep­tors. These help the sig­nal con­ti­nue on the oth­er side.


A key neurotrans­mitter, glu­ta­mate, binds to pro­teins known as AMPA re­cep­tors, em­bed­ded in the den­drit­ic spines on the re­ceiv­ing cells. These re­cep­tors are one of two re­cep­tor types known to play a cru­cial role in learn­ing and mem­o­ry, Bresloff said. The AMPA re­cep­tors, he added, are held in the mem­brane cov­er­ing the cell by oth­er mo­le­cules called scaf­fold­ing pro­teins.


Ear­li­er re­search in­di­cates learn­ing and mem­o­ry de­pend on the strength of syn­apses. Bress­loff said a syn­apse’s strength de­pends not on­ly on how much neu­ro­trans­mitter the up­stream cell sends, but on oth­er fac­tors, in­clud­ing the num­ber of re­cep­tors like AMPA.


Bress­lof­f studied how syn­apse strength re­lates to the num­ber of AMPA re­cep­tors, which helps de­ter­mine the strength of a trans­mitted cur­rent.


In­di­vid­u­al re­cep­tors con­stantly are re­cy­cled or “traf­ficked” in and out of the syn­apse, he said. How can the ever-changing syn­apse help re­tain learn­ing and mem­o­ries? He creat­ed a math­e­mat­i­cal sim­u­la­tion to de­scribe re­cep­tor move­ments based on the idea that the re­ceiv­ing, mush­room-shaped den­drit­ic spine has two com­part­ments. One looks like the mush­room cap; it’s where scaf­fold­ing pro­teins pin re­cep­tors in place so they can re­ceive glu­ta­mate’s chem­i­cal sig­nal. The sec­ond com­part­ment is like the mush­room’s stalk.


Bress­loff used equa­tions to de­scribe how quick­ly re­cep­tors leave or en­ter a syn­apse by go­ing be­tween the “cap” and “stalk.” The equa­tions sug­gested that the big­gest fac­tor in strength­en­ing syn­apses was the scaf­fold­ing pro­teins. “You can’t just shove a bunch of new AMPA re­cep­tors to the sur­face be­cause they will just go away again,” he said; “you need to keep them there.” What we remem­ber and learn is in ef­fect, he ar­gued, an­chored to nerve cells.

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