Editing Barrel cortex (section)

==Experience-dependent plasticity==

Because the barrel cortex has a well-organised structure that relates clearly to the whisker pad, it has been used extensively as a tool to study sensory processing and development, and the phenomenon of experience-dependent plasticity - changes in the activity, connectivity, and structure of neural circuits in response to experience. Neurons in the barrel cortex exhibit the property of [[synaptic plasticity]] that allows them to alter the vibrissae to which they respond depending on the rodent's history of tactile experience.<ref>Hardingham N, Glazewski S, Pakhotin P, Mizuno K, Chapman PF, Giese KP, Fox K. Neocortical long-term potentiation and experience-dependent synaptic plasticity require alpha-calcium/calmodulin-dependent protein kinase II auto-phosphorylation. J Neurosci. 2003 Jun 1;23(11):4428-36.</ref> Experience-dependent plasticity is commonly studied in the barrel cortex by partially depriving it of sensory input, either by lesioning elements of the afferent pathway (e.g. the trigeminal nerve) or by ablating, plucking, or trimming some of the facial whiskers. The anatomical structure of the barrels is only affected by lesioning elements of the pathway, but innocuous forms of deprivation can induce rapid changes in the cortical map into adulthood, without any corresponding changes in the barrel structures.<ref>{{cite journal | author = Fox K | year = 2002 | title = Anatomical pathways and molecular mechanisms for plasticity in the barrel cortex | journal = Neuroscience | volume = 111 | issue = 4| pages = 799–814 | doi=10.1016/s0306-4522(02)00027-1| pmid = 12031405 | s2cid = 39423181 }}</ref> Because of their different effects, it seems these two paradigms work by different mechanisms.

Some forms of plasticity in the barrel cortex display a [[critical period]]. Plucking whiskers in neonatal rats causes a long-lasting expansion of the representation of the spared whisker in layer 4.<ref>{{cite journal | author = Fox K | year = 1992 | title = A critical period for experience-dependent synaptic plasticity in rat barrel cortex | journal = J Neurosci | volume = 12 | issue = 5| pages = 1826–1838 | doi = 10.1523/JNEUROSCI.12-05-01826.1992 | pmid = 1578273 | pmc = 6575898 | doi-access = free }}</ref> However, layer 4 plasticity rapidly diminishes if sensory deprivation begins after day 4 of life (P4) whereas representations in layer 2/3 remain highly plastic into adulthood.<ref name=glazewski96>{{cite journal | author = Glazewski S, Fox K | year = 1996 | title = Time course of experience-dependent synaptic potentiation anddepression in barrel cortex of adolescent rats | journal = J Neurophysiol | volume = 75 | issue = 4| pages = 1714–1729 | doi = 10.1152/jn.1996.75.4.1714 | pmid = 8727408 }}</ref><ref>{{cite journal | vauthors = Stern EA, Maravall M, Svoboda K |author3-link=Karel Svoboda (scientist) | year = 2001 | title = Rapid development and plasticity of layer 2/3 maps in rat barrel cortex in vivo | journal = Neuron | volume = 31 | issue = 2| pages = 305–315 | doi=10.1016/s0896-6273(01)00360-9| pmid = 11502260 | s2cid = 2819415 | doi-access = free }}</ref>

Two cortical processes run alongside each other when barrel cortex is deprived of sensory input from some whiskers to produce representational plasticity. In deprived cortex, neuronal responses to spared whiskers are enhanced and responses to deprived whiskers are weakened. These two processes have different time courses, with the weakening of deprived response preceding the strengthening of spared response, implying that they have different underlying mechanisms. These two effects combine to produce an expansion of the cortical representation of spared whiskers into the representation of adjacent deprived whiskers.<ref name=glazewski96 /><ref name=feldman>{{cite journal | author = Feldman DE, Brecht M | s2cid = 2892382 | year = 2005 | title = Map plasticity in somatosensory cortex | journal = Science | volume = 310 | issue = 5749| pages = 810–815 | doi=10.1126/science.1115807| pmid = 16272113 }}</ref>

It is likely that several different mechanisms are involved in producing experience-dependent
plasticity in a whisker deprivation protocol (adapted from Feldman and Brecht, 2005<ref name=feldman /> ):

#Almost immediately, loss of input to a deprived barrel column leads to a loss of inhibitory firing in that column. This unmasks horizontal excitatory connections from adjacent spared columns.<ref>{{cite journal |vauthors=Kelly MK, Carvell GE, Kodger JM, Simons DJ |title=Sensory loss by selected whisker removal produces immediate disinhibition in the somatosensory cortex of behaving rats |journal=J. Neurosci. |volume=19 |issue=20 |pages=9117–25 |year=1999 |pmid=10516329 |doi=10.1523/JNEUROSCI.19-20-09117.1999 |pmc=6782760 }}</ref> This does not explain longer-lasting plastic changes as the unmasking would disappear immediately if the deprived input was reinstated (for example by allowing the whisker to regrow).
#[[Long-term potentiation|LTP]]- and [[Long-term depression|LTD]]-like processes also seem to be involved. This can be inferred by using transgenic mice where there are changes in the expression of enzymes related to LTP and LTD e.g. calmodulin-dependent protein kinase II (CaMKII) or cyclic-AMP response element binding protein (CREB). In these mice, plasticity is compromised<ref>{{cite journal | vauthors = Glazewski S, Chen CM, Silva A, Fox K | year = 1996 | title = Requirement for alpha-CaMKII in experience dependent plasticity of the barrel cortex | journal = Science | volume = 272 | issue = 5260| pages = 421–423 | doi=10.1126/science.272.5260.421| pmid = 8602534 | bibcode = 1996Sci...272..421G | s2cid = 84433995 }}</ref><ref>{{cite journal | vauthors = Glazewski S, Barth AL, Wallace H, McKenna M, Silva A, Fox K | year = 1999 | title = Impaired experiencedependent plasticity in barrel cortex of mice lacking the alpha and delta isoforms of CREB | journal = Cereb Cortex | volume = 9 | issue = 3| pages = 249–256 | doi=10.1093/cercor/9.3.249| pmid = 10355905 | doi-access = free }}</ref> Spike timing rather than frequency may be an important factor. Associative LTP has been demonstrated at layer 4 to layer 2/3 synapses when the layer 4 neuron fires 0-15 ms before the layer 2/3 neuron, and LTD is observed when this timing order is reversed.<ref>{{cite journal | vauthors = Feldman DE | year = 2000 | title = Timing-based LTP and LTD at vertical inputs to layer II/III pyramidal cells in rat barrel cortex | journal = Neuron | volume = 27 | issue = 1| pages = 45–56 | doi=10.1016/s0896-6273(00)00008-8 | pmid=10939330| s2cid = 17650728 | doi-access = free }}</ref> Such mechanisms could act rapidly to produce plastic changes within hours or days.
#Sensory deprivation has been demonstrated to cause changes in synaptic dynamics such as [[Excitatory postsynaptic potential|EPSP]] amplitude and frequency. The net effect of these changes is to increase the proportion of synaptic input which layer 2/3 neurons in deprived barrels receive from spared barrels.<ref>{{cite journal | vauthors = Finnerty GT, Roberts LS, Connors BW | year = 1999 | title = Sensory experience modifies the short-term dynamics of neocortical synapses | journal = Nature | volume = 400 | issue = 6742| pages = 367–371 | doi = 10.1038/22553 | pmid = 10432115 | bibcode = 1999Natur.400..367F | s2cid = 4413560 }}</ref> These observations suggest that other, more specific, mechanisms besides LTP/LTD are at play in experience-dependent plasticity.
#It seems intuitively likely that structural changes at the level of axons, dendrite branches, and dendrite spines underlie some of the long-term plastic changes in the cortex. Changes in axon structure have been reported in plasticity following lesions <ref>{{cite journal | vauthors = Chklovskii DB, Mel BW, Svoboda K | year = 2004 | title = Cortical rewiring and information storage | journal = Nature | volume = 431 | issue = 7010| pages = 782–788 | doi=10.1038/nature03012 | pmid=15483599| bibcode = 2004Natur.431..782C | s2cid = 4430167 }}</ref>  and more recently by studies using whisker trimming.<ref name=cheetham2008>Cheetham CE, Hammond MS, MacFarlane R, Finnerty GT (2008) Altered sensory experience induces targeted rewiring of local excitatory connections in mature neocortex. J Neurosci (in press).</ref> Dendritic branching is important during prenatal and neonatal development, is involved in  plasticity induced by lesions, but is not involved in experience-dependent plasticity.<ref name=tracht>{{cite journal | vauthors = Trachtenberg JT, Chen BE, Knott GW, Feng G, Sanes JR, Welker E, Svoboda K | year = 2002 | title = Long-term in vivo imaging of experience-dependent synaptic plasticity in adult cortex | journal = Nature | volume = 420 | issue = 6917| pages = 788–794 | doi=10.1038/nature01273| pmid = 12490942 | bibcode = 2002Natur.420..788T | s2cid = 4341820 }}</ref> In vivo two-photon microscopy reveals that dendritic spines in mouse barrel cortex are highly dynamic and subject to continuous turnover, and may be associated with formation or deletion of synapses.<ref name=tracht /> It is likely that spine turnover is necessary but not sufficient to produce experience-dependent plasticity, and other mechanisms such as axonal remodelling are also needed to explain features such as savings from prior experience.<ref name=cheetham2008 />

Plasticity and remodelling of barrel cortex has also been studied in the context of [[traumatic brain injury#Sensory_processing|traumatic brain injury]],<ref>{{cite journal |title= Carron SF, Alwis DS, Rajan R. Traumatic Brain Injury and Neuronal Functionality Changes in Sensory Cortex. Front Syst Neurosci. 2016;10(June):47. doi:10.3389/fnsys.2016.00047.| journal=Frontiers in Systems Neuroscience| year=2016| volume=10| doi=10.3389/fnsys.2016.00047| last1=Carron| first1=Simone F.| last2=Alwis| first2=Dasuni S.| last3=Rajan| first3=Ramesh| page=47| pmid=27313514| pmc=4889613| doi-access=free}}</ref> where environmental enrichment of stimuli has been shown to induce plasticity/recovery <ref>{{cite journal| title=Alwis DS, Yan EB, Johnstone V, et al. Environmental enrichment attenuates traumatic brain injury: Induced neuronal hyperexcitability in supragranular layers of sensory cortex. J Neurotrauma. 2016;33(11). doi:10.1089/neu.2014.3774.|year=2016|pmid=26715144|url=https://pubmed.ncbi.nlm.nih.gov/26715144/|last1=Alwis|first1=D. S.|last2=Yan|first2=E. B.|last3=Johnstone|first3=V.|last4=Carron|first4=S.|last5=Hellewell|first5=S.|last6=Morganti-Kossmann|first6=M. C.|last7=Rajan|first7=R.|journal=Journal of Neurotrauma|volume=33|issue=11|pages=1084–1101|doi=10.1089/neu.2014.3774}}</ref> and patterns of temporal coding have been altered via plasticity and recovery mechanisms.<ref>{{Cite thesis| title= Burns (2019) Temporal neuronal activity patterns in barrel cortex to simple and complex stimuli and the effects of traumatic brain injury. Monash University. Thesis. 10.26180/5b7166ad13e47 | year=2019| doi=10.26180/5b7166ad13e47| url=https://doi.org/10.26180/5b7166ad13e47| author1=THOMAS FRANCIS BURNS| publisher=Monash University| type=thesis}}</ref>