Differentiation of Hebbian and homeostatic plasticity mechanisms within layer 5 visual cortex neurons

Abstract

Cortical layer 5 contains two major types of projection neuron known as IB (intrinsic bursting) cells that project sub-cortically and RS (regular spiking) cells that project between cortical areas. This study describes the plasticity properties of RS and IB cells in the mouse visual cortex during the critical period for ocular dominance plasticity. We find that RS neurons exhibit synaptic depression in response to both dark exposure (DE) and monocular deprivation (MD), and their homeostatic recovery from depression is dependent on TNF-α. In contrast, IB cells demonstrate opposite responses to DE and MD, potentiating to DE and depressing to MD. IB cells' potentiation depends on CaMKII-autophosphorylation and not TNF-α. IB cells show mature synaptic properties at the start of the critical period while RS cells mature during the critical period. Together with observations in somatosensory cortex, these results suggest that differences in RS and IB plasticity mechanisms are a general cortical property.

Keywords: CP: Neuroscience; CaMKII; LTD; LTP; TNF-α; cortico-cortical; dark-exposure; development; mEPSC; monocular-deprivation; subcortical.

Graphical abstract

Figure 1

IB and RS neuronal properties (A) Example morphology of electrophysiologically identified IB and RS cells. Scale bars, 100 μm. The spike discharges are produced from somatic current injection. Scale bars, 20 mV and 100 ms (spike discharges) and 20 pA and 100 ms (current injection). (B) Sholl plots for apical tuft, oblique, and basal dendrites from RS (black) and IB cells (red). RS neurons have significantly fewer branches than IB cells at apical tuft (t₍₂₀₎ = 5.03, p < 0.0001) apical oblique (t₍₂₀₎ = 2.87, p < 0.01), and basal dendritic locations (t₍₂₀₎ = 3.13, p < 0.01). Data points represent means ± SEM. See also Figures S1 and S2 for further distinctions between RS and IB cells.

Figure 2

Synaptic development of layer 5 RS and IB neurons (A) Example mEPSC traces and cumulative distribution functions (CDFs) for RS cells in the P27-32 (blue) and P33-38 (black) age group. Scale bars, 10 pA and 250 ms. The CDFs for the two age groups are significantly different (p < 0.001, see results). Data points represent means ± SEM. (B) Example mEPSC traces and CDFs for IB cells in the P27-32 (blue) and P33-38 (black) age group. Scale bars, 10 pA and 250 ms. The CDFs for the two age groups are not significantly different (p = 0.65, see results). (C and D) RS cells show a decrease in synaptic efficacy between P27 and P38 (linear regression, p < 0.01), whereas (D) IB cells show no change over this period (linear regression, p = 0.42; see text for statistics). Each data point represents a single cell.

Figure 3

Effect of monocular deprivation on synaptic strength in layer 5 RS and IB cells (A) Example mEPSCs and time course of change in RS cells’ mEPSCs following monocular deprivation. Scale bars, 10 pA and 250 ms. (B) CDFs for control and the two significantly depressed time points shown in (A) at 12 h (red) and 3 days (blue). (C) Example mEPSC traces and time course of changes in IB cells’ mEPSCs following monocular deprivation. Scale bars, 10 pA and 250 ms. (D) CDFs for the 5-day time point (blue) compared with control (black). ^∗p < 0.05, ^∗∗p < 0.01. Data points represent means ± SEM. (See Figure 1, Figure 2, Figure 3, Figure 4, Figure 5, Figure 6 for CDFs of all time points). See also Figure S6.

Figure 4

Effect of dark exposure on synaptic strength in layer 5 RS and IB cells (A) Example mEPSC traces and time course of change in RS cells’ mEPSCs following dark exposure. Scale bars, 10 pA and 250 ms. (B) CDFs for control (black) and the 12 h DE (blue) significantly depressed time point shown in (A). Scale bars, 10 pA and 250 ms. (C) Example mEPSC traces and time course of changes in IB cells’ mEPSCs following dark exposure. (D) CDFs for the 3-day DE (blue) and 5-day DE (red) time points. ^∗p < 0.05, ^∗∗p < 0.01. Data points represent means ± SEM. (See Figure 1, Figure 2, Figure 3, Figure 4, Figure 5, Figure 6 for all CDFs). See also Figure S6.

Figure 5

RS and IB neurons show different plasticity mechanisms during dark exposure (A and B) Depression and homeostatic rebound to baseline values in wild-type cells (black) and CaMKII t286a mutants (blue) are similar in RS cells (A), whereas homeostatic rebound does not occur in wild-type RS cells treated with TNF-α inhibitor (red) (B). (C and D) Potentiation does not occur in IB cells of CaMKII-t286a mutants (blue) (C); however, potentiation is unaffected by treatment with TNF-α inhibitor (red) (D). Data points represent means ± SEM. (∗ indicates p < 0.05 and ∗∗∗p < 0.001)

Figure 6

Changes in spine head diameter following dark exposure (A) In IB cells, spine head size increases for spines on basal dendrites after 12 h of dark exposure (blue). (B) Significant changes in spine head size could not be detected in RS cells following DE. (C) CDFs for basal dendritic spines from IB cells show that the increase in IB spine head size after 12 h DE (blue) is uniform across the population of spines. (D) Spine head sizes show a scaling difference between apical (red) and basal (blue) spines from IB cells. (E) Example dendritic spines on basal dendrites of IB neurons from a control animal (Ei); basal dendrites of IB neurons from an animal after 12 h DE (Eii). (F) Basal dendrites of an IB neuron from a control animal (Fi), (apical dendrite of an IB neuron from a control animal (Fii). Scale bar, 2 μm (in spines images). Data points represent means ± SEM. See also Figure S6.