Bagong pananaliksik ay ipinapakita ang cellular mekanismo na kung saan memory-encoding neuronal network sumulpot
Sabihin mo sa akin kung saan tumira ang mga saloobin, nakalimutan hanggang tawagan mo sila balik? Sabihin mo sa akin kung saan tumira ang joys ng lumang, at kung saan ang mga sinaunang loves, At kapag sila ay i-renew muli, at ang gabi ng limot nakalipas, Upang aking pagtawid beses at puwang malayo remote, at dalhin Comforts sa isang kasalukuyan kalungkutan at isang gabi ng sakit? Saan ka paroroon, O pag-iisip? Upang kung ano ang remote lupa ang iyong flight? Kung returnest ikaw hanggang sa kasalukuyan sandali ng kapighatian, Iuuwi mo ba comforts sa iyong mga pakpak, at hamog at pulot, at mga balsamo, O lason mula sa wilds disyerto, mula sa mga mata ng pangingimbulo?
Sa kanyang mahabang tula tula, Visions ng Daughters of Albion, William Blake kababalaghan tungkol sa likas na katangian ng memory, kanyang kakayahan sa itak transportasyon sa amin sa malayong mga oras at lugar, at ang malakas na damdamin, parehong positibo at negatibong, na ang aming mga recollections maaaring pukawin. Ang tula ay naglalaman ng mga katanungan na mananatiling mataas na may kinalaman sa araw na ito, tulad ng kung ano ang nangyayari sa ating pang-nawalang mga alaala, at paano makuha namin ang mga ito?
Higit sa dalawang siglo mamaya, ang mga mekanismo ng memory imbakan at pagsasauli ay ang pinaka-intensively-aral phenomena sa siyensiya utak. Malawak Ito ay naniniwala na ang memorya ng bituin ay nagsasangkot ng pagpapalakas ng koneksyon sa pagitan ng sparsely ipinamamahagi network ng mga neurons sa isang istraktura utak na tinatawag na hippocampus, at ang mga kasunod na pagbawi ay nagsasangkot reactivation ng parehong neuronal ensembles. gayunman, neuroscientists still struggle to answer Blake’s questions definitely.
Ngayon, a team of researchers at the University of Geneva have made another important advance in our understanding of the neural mechanisms underlying memory formation. Using a state-of-the-art method called optogenetics, they show how the neuronal ensembles that encode memories emerge, revealing that ensembles containing too many neurons – or too few – impair memory retrieval.
Optogenetics is an extremely powerful technique that involves introducing algal proteins called channelrhodopsins (ChRs) into neurons. This renders the cells sensitive to light, such that specified groups of them can be switched on or off, using pulses of laser light delivered into the brain via optical fibres, on a timescale of milliseconds.
In recent years, researchers have used optogenetics to label hippocampal neurons that become active during memory formation in the mouse brain, and to manipulate the labelled ensembles in various ways. In this way, they can reactivate the same ensembles to induce memory retrieval; switch fearful memories on or off; convert negative memories into positive ones, or vice versa; and even implant entirely false memories into the brains of mice.
The new research, led by Pablo Mendez and the late Dominique Muller, who tragically died in a gliding accident in April of last year, builds on this earlier work. They created genetically engineered mice expressing ChR in granule cells on one side of the brain, in the dentate region of the hippocampus. Granule cells are the principle neurons in this region of the hippocampus, which are thought to be critical for hippocampal functions such as memory and spatial navigation. They placed the animals into large cages, allowing some of them to explore their new environment. Samantala, they optogenetically activated random granule cells in some of the mice, but not others.
When they dissected and examined the animals’ brains 45 minutes later, the researchers found spatial exploration evoked activity in ensembles of hippocampal neurons, as determined by levels of cFos, a so-called ‘immediate early’ gene that is switched on quickly when neurons start to fire. mahalaga, mice allowed to explore their cages had higher numbers of cFos-expressing granule cells than those left in their home cages for the duration of the experiment, and those that received optogenetic stimulation during the exploration had significantly higher numbers of cFos–positive neurons than those that did not.
This showed that spatial exploration evokes activity in ensembles of dentate granule cells, and that randomly altering the activity of these networks with optogenetic stimulation increases the size of the ensembles, or the number of cells within them.
But does manipulating the size of the ensembles have any effect on behaviour? To find out, Mendez and his colleagues placed mice expressing ChR in their hippocampi into another cage, and gave them several mild electric shocks. With repetition of this treatment, the mice quickly learn to fear the cage, and quickly freeze up when returned into it, even when they are not given more shocks.
This time, the researchers optogenetically stimulated random granule cells in some of the mice, but not others, during the training, in order to increase the size of the neuronal ensemble that encodes the fearful memory. These mice exhibited less freezing behaviour when returned to the same cage than others who received no stimulation. But the stimulation also created artificial fear memories, such that the animals froze up in other situations, masyado.
Inhibition of random granule cells had the same effect, suggesting that merely altering the number of neurons in the ensemble interfered with the animals’ ability to recall the fearful memories. These findings are consistent with those of an earlier study, which also showed that inhibiting or stimulating granule cell activity impairs contextual learning.
To understand why this might be, the researchers performed another series of experiments, using microelectrodes to record the activity of neurons in slices of hippocampal tissue. These experiments showed that optogenetic stimulation of granule cells produces a robust response in neighbouring interneurons, which release the inhibitory neurotransmitter GABA.
kaya, the firing of granule cells leads inhibitory interneurons, which dampen adjacent granule cells and prevent them from entering the ensemble. In this way, interneurons appear to stabilize newly-formed memories by regulating the number and distribution of granule cells involved in encoding memories. Activating or silencing random granule cells upsets this process and alters the number of granule cells, which may make the new memories unstable.
“In this study, we used a simple form of memory, the memory of a spatial context, but the challenge is studying how more complex experiences are memorized, and how the brain deals with the storage of multiple experiences,” says Mendez. “Understanding these questions could help us to understand the limits of the brain’s storage capacity.”
Stefanelli, T., et al. (2016). Hippocampal Somatostatin Interneurons Control the Size of Neuronal Memory Ensembles. neuron, 89: 1-12. DOI: 10.1016/j.neuron.2016.01.024 [abstract]
guardian.co.uk © Tagapangalaga News & Media Limited 2010