Kaylee Kearsley Slcc 1615 Bio Lab Friday, 10:00 a.m. Prof. Jack T.

Later

Experience Dependent Rewiring of Specific Connections in Adult Neocortex

Scientists wanted to know if specific input had specific wiring motifs to different parts of the neocortex, is placticity limited to specific critical developmental period or does it continue into adult hood, and is motif repair specific or is circuit repair broader. In order to answer these questions scientists performed a series of sensory deprivation experiments along with experiments after regrowth of sensory cortex was complete. Scientists performed a series of experiments on mice that were bred specifically for this experiment. The mice were raised beyond the critical psychological developmental stage that all animals undergo. The purpose of them reaching an adult level of maturity is to show if the neocortex of adult animals have the same plasticity and ability to create or rewire synapse of sensory input as they did during the critical period. Mice were kept in a controlled environment: Top open cages on a 12 hr light/dark cycle and fed a custom diet. Mice were all genetically similar and homozygous for certain traits. At age 8-10 week period whiskers in rows A, B, D, and E on the right side were trimmed every other day for 2-3 weeks. Whisker trimming was performed under an anesthesia of ketamine and medetomidin. Control animals underwent the same anesthesia treatment. Scientists removed the brains of the mice at different stages of the experiment. Slices of deprived mice were harvested no later than 36 hours after the last whisker trimming session. For scientists to see the effects of recovery after whisker deprivation, scientists allowed a 4-5 week regrowth period and a 12-14 week regrowth period. In order to see the synapse and interneuron firing rate scientists used Electrophysiology and Optical Stimulation.

Electrophysiology and Optical Stimulation: Mice were anesthetized by an

injection of ketamine and medetomidin and perfused cardally with an ice cold solution. The brain was recovered. Then slices of the left primary somatosensory cortex were cut. The slices were cut at at 45 degree angle to maintain a field along the barrel whisker rows. Then recordings were amplified from a voltage clamp. A continuous lazer excited sensory pathways and were recorded at each of the different levels of whisker deprivation and regrowth.

Scientist allowed a whisker regrowth period of about 3 months until whiskers were completely regrown. Scientists then removed the brains of the mice for further experimentation. The same experiments were done on the mice whose whiskers were allowed to regrow and compared to the original batch of mice. Scientists checked the firing rate and pathway through Axonal Morphometry.

Axonal Morphometry: Slices of the brain were incubated in a modified cerebral

spinal fluid for an hour then overnight in a different solution. The slices were then put through a series of staining rinses then mounted in VectaShield and then imaged on a Leica TCS SP5 confocal microscope and studied for the density of synapse. Scientists noticed that specific inhibitory synapse had many Buttons that connect or lead to a certain action, or sensory input. Scientist predicted that when mice undergo whisker deprivation that the buttons would diminish. And along with the different but tons diminishing, they thought that the firing rate and intensity of the axon would too. In a sense they were right. After studying the mice that underwent whisker deprivation but not allowed the full recovery period they noticed there were far less synapses which led to less electric flow through the axon potential, shown through a weaker signal in Axonal Morphometry. They compared this to mice able to finish regrowth of whiskers and saw that they elicited the same signal as before whisker deprivation. This showed them that the synapse fully recovered their ability to signal sensory input. After comparing complete sensory deprivation to absolutely no deprivation, scientists decided to run tests on mice that underwent partial whisker deprivation (selective whiskers were trimmed). They found that when mice underwent partial whisker deprivation the Synapse density increased in neighbor whiskers and that even though buttons were lost for the time being synapse density allowed for the strength of the current or signal to remain the same. The density made up for the loss of the whisker, and sensory input was unaffected. After the regrowth period scientists performed all the same experiments on the signal strength and found that all the buttons and synapse for sensory input was completely restored. This showed them that even though they underwent profound sensory changes, that the brain was able to adapt to the change and was also able to repair its damaged synapse and create synaptic pathways for sensory input. Scientist were able to determine that even after the critical developmental period for all animals that the brain has the ability to repair and restore original synapse and to create new synapse to change and adapt with the environment around it.

The critical developmental stage isnt as critical as it is made out to be because through all of the sensory deprivation and recovery of the sensory input motifs, the input signal shown in Electrophysiology and Optical Stimulation ended up being the same as the undeprived mice. This, in a sense, proves that you can teach an old dog new trick. The adult neocortex has the ability to adapt and change and create synaptic pathways just as a developing neocortex does as it is introduced in to the worlds vast sensory eliciting stimuli. The placisticy is universal to all neocortex. Though it has been introduced to a variety of stimuli already, the adult neocortex is always changing, repairing, evolving, and learning. Damage to sensory organs is now proved to be reversible. The only drawback to this is the severing of optical pathways. Sensory pathways cannot always be repaired when damage is done to the eye. Scientist are still experimenting on this subject and still have many questions to answer.

Refrences http://plosbiology.org/article/info%3Adoi%2f10.1371%2f journal.pbio.1001798