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Experience-Dependent, Layer-Specific Development of Divergent Thalamocortical Connectivity.

Crocker-Buque A, Brown SM, Kind PC, Isaac JT, Daw MI - Cereb. Cortex (2014)

Bottom Line: Here, we show that, in neonates, the input to layer 6 is as strong as that to layer 4.This strengthening consists of an increase in axon branching and the divergence of connectivity in layer 4 without a change in the strength of individual connections.We propose that experience-driven LTP stabilizes transient TC synapses in layer 4 to increase strength and divergence specifically in layer 4 over layer 6.

View Article: PubMed Central - PubMed

Affiliation: Centre for Integrative Physiology, University of Edinburgh, Edinburgh, UK.

No MeSH data available.


Development of TC Input to L4 and L6. Diagrammatic representation of findings showing the speeding of L4 TC EPSP kinetics and increase in amplitude resulting from LTP and an increase in the number of L4 cells contacted by each TC axon and the lack of relative change in L6 TC EPSP properties. The inset above shows that temporary synaptic contacts are made repeatedly in L4 during the P3–P5 period and only retained if that synapse undergoes LTP.
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BHU031F8: Development of TC Input to L4 and L6. Diagrammatic representation of findings showing the speeding of L4 TC EPSP kinetics and increase in amplitude resulting from LTP and an increase in the number of L4 cells contacted by each TC axon and the lack of relative change in L6 TC EPSP properties. The inset above shows that temporary synaptic contacts are made repeatedly in L4 during the P3–P5 period and only retained if that synapse undergoes LTP.

Mentions: How can LTP mediate this increase in the number of TC axons contacting each cell? One explanation is that TC axons could make transient contacts preferentially onto cells which they do not already innervate, perhaps as immature synapses with slow kinetics (Kidd and Isaac 1999; Bannister et al. 2005). In this scheme, LTP would both convert these synapses to fast synapses and stabilize them against future elimination (Fig. 8). Further contacts requiring stabilization would then be made onto new cells. As such the decrease in the proportion of immature slow synapses (Kidd and Isaac 1999; Bannister et al. 2005) represents a developmental decrease in the number of new, transient contacts being formed, and the increase in the number of TC axons contacting each L4 cell is the result of multiple rounds of synapse stabilization by LTP. Whisker trimming did not result in an increased incidence of immature slow synapses at P8–P9 (data not shown), suggesting that the time period in which such transient contacts are formed is predetermined and this acts as the substrate for experience-dependent plasticity. Alternatively, or in parallel, temporary contacts may be mediated by NMDA-only silent synapses (Isaac et al. 1997). Silent synapses also decrease in number throughout the age range of this study, although we did not examine whether whisker trimming affected the developmental profile of silent synapse expression. Additionally, it is likely that we slightly underestimate the connectivity at P3–P5 as we did not test for silent synapses; however, this does not alter the finding that there was a large increase in the number of cells contacted by synapses functional at resting potential. Recently described potentiation of TC connections induced beyond the canonical critical period in response to adult sensory deprivation results in an increase in both mEPSC and msEPSC amplitude, suggesting that a separate mechanism is activated under these adult conditions (Yu et al. 2012). Our model is consistent with findings in the visual cortex in which light exposure in dark-reared mice initially results in an increase in spine turnover and motility (Tropea et al. 2010); equivalent to the turnover of transient synapses we propose in the barrel cortex. After 1 week of light exposure, spine turnover and motility decreases (Tropea et al. 2010) which could represent synapse stabilization by LTP. Furthermore, our data show that each TC axon is connected to approximately 50% of neighboring L4 cells. Anatomically individual TC axons branch extensively throughout the entire barrel without bias to one region (Jensen and Killackey 1987), suggesting that this highly divergent TC connectivity is retained throughout the entire barrel consistent with estimates of TC connectivity from in vivo recordings in adults (Bruno and Simons 2002). This similarity suggests that there is unlikely to be further experience-dependent increase in TC-L4 connectivity in animals older than those studied here. We cannot rule out, however, that there are later increases in the strength of TC input to L5B or L6. Such an increase may be implied from the demonstration in adult rats that L5B and L6 cells are strongly and directly activated by the thalamus in vivo (Constantinople and Bruno 2013). This study, however, also reports smaller sensory PSPs to deep layers than to L4 with a high level of sensory-evoked spikes in L5B attributed to resting potentials closer to threshold than in L4, so the adult phenotype may not require further experience-dependent alteration.Figure 8.


Experience-Dependent, Layer-Specific Development of Divergent Thalamocortical Connectivity.

Crocker-Buque A, Brown SM, Kind PC, Isaac JT, Daw MI - Cereb. Cortex (2014)

Development of TC Input to L4 and L6. Diagrammatic representation of findings showing the speeding of L4 TC EPSP kinetics and increase in amplitude resulting from LTP and an increase in the number of L4 cells contacted by each TC axon and the lack of relative change in L6 TC EPSP properties. The inset above shows that temporary synaptic contacts are made repeatedly in L4 during the P3–P5 period and only retained if that synapse undergoes LTP.
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Related In: Results  -  Collection

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BHU031F8: Development of TC Input to L4 and L6. Diagrammatic representation of findings showing the speeding of L4 TC EPSP kinetics and increase in amplitude resulting from LTP and an increase in the number of L4 cells contacted by each TC axon and the lack of relative change in L6 TC EPSP properties. The inset above shows that temporary synaptic contacts are made repeatedly in L4 during the P3–P5 period and only retained if that synapse undergoes LTP.
Mentions: How can LTP mediate this increase in the number of TC axons contacting each cell? One explanation is that TC axons could make transient contacts preferentially onto cells which they do not already innervate, perhaps as immature synapses with slow kinetics (Kidd and Isaac 1999; Bannister et al. 2005). In this scheme, LTP would both convert these synapses to fast synapses and stabilize them against future elimination (Fig. 8). Further contacts requiring stabilization would then be made onto new cells. As such the decrease in the proportion of immature slow synapses (Kidd and Isaac 1999; Bannister et al. 2005) represents a developmental decrease in the number of new, transient contacts being formed, and the increase in the number of TC axons contacting each L4 cell is the result of multiple rounds of synapse stabilization by LTP. Whisker trimming did not result in an increased incidence of immature slow synapses at P8–P9 (data not shown), suggesting that the time period in which such transient contacts are formed is predetermined and this acts as the substrate for experience-dependent plasticity. Alternatively, or in parallel, temporary contacts may be mediated by NMDA-only silent synapses (Isaac et al. 1997). Silent synapses also decrease in number throughout the age range of this study, although we did not examine whether whisker trimming affected the developmental profile of silent synapse expression. Additionally, it is likely that we slightly underestimate the connectivity at P3–P5 as we did not test for silent synapses; however, this does not alter the finding that there was a large increase in the number of cells contacted by synapses functional at resting potential. Recently described potentiation of TC connections induced beyond the canonical critical period in response to adult sensory deprivation results in an increase in both mEPSC and msEPSC amplitude, suggesting that a separate mechanism is activated under these adult conditions (Yu et al. 2012). Our model is consistent with findings in the visual cortex in which light exposure in dark-reared mice initially results in an increase in spine turnover and motility (Tropea et al. 2010); equivalent to the turnover of transient synapses we propose in the barrel cortex. After 1 week of light exposure, spine turnover and motility decreases (Tropea et al. 2010) which could represent synapse stabilization by LTP. Furthermore, our data show that each TC axon is connected to approximately 50% of neighboring L4 cells. Anatomically individual TC axons branch extensively throughout the entire barrel without bias to one region (Jensen and Killackey 1987), suggesting that this highly divergent TC connectivity is retained throughout the entire barrel consistent with estimates of TC connectivity from in vivo recordings in adults (Bruno and Simons 2002). This similarity suggests that there is unlikely to be further experience-dependent increase in TC-L4 connectivity in animals older than those studied here. We cannot rule out, however, that there are later increases in the strength of TC input to L5B or L6. Such an increase may be implied from the demonstration in adult rats that L5B and L6 cells are strongly and directly activated by the thalamus in vivo (Constantinople and Bruno 2013). This study, however, also reports smaller sensory PSPs to deep layers than to L4 with a high level of sensory-evoked spikes in L5B attributed to resting potentials closer to threshold than in L4, so the adult phenotype may not require further experience-dependent alteration.Figure 8.

Bottom Line: Here, we show that, in neonates, the input to layer 6 is as strong as that to layer 4.This strengthening consists of an increase in axon branching and the divergence of connectivity in layer 4 without a change in the strength of individual connections.We propose that experience-driven LTP stabilizes transient TC synapses in layer 4 to increase strength and divergence specifically in layer 4 over layer 6.

View Article: PubMed Central - PubMed

Affiliation: Centre for Integrative Physiology, University of Edinburgh, Edinburgh, UK.

No MeSH data available.