Unbiased methods to assess the firing activity of individual neurons in the neocortex have revealed that a large proportion of cells fire at extremely low rates (<0.1 Hz), both in their spontaneous and evoked activity. Thus, firing in neocortical networks appears to be dominated by a small population of highly active neurons. Here we use a fosGFP transgenic mouse to examine the properties of cells with a recent history of elevated activity. FosGFP-expressing layer 2/3 pyramidal cells fired at higher rates compared to fosGFP− neurons, both in vivo and in vitro. Elevated activity could be attributed to increased excitatory and decreased inhibitory drive to fosGFP+ neurons. Paired-cell recordings indicated that fosGFP+ neurons had a greater likelihood of being connected to each other. These findings indicate that highly active, interconnected neuronal ensembles are present in the neocortex and suggest these cells may play a role in the encoding of sensory information.
Critical periods for experience-dependent plasticity have been well-characterized within sensory cortex, where the ability of altered sensory input to drive firing rate changes has been demonstrated across brain areas. Here we show that rapid experience-dependent changes in the strength of excitatory synapses within mouse primary somatosensory cortex exhibit a critical period that is input-specific and mechanistically distinct in layer 2/3 pyramidal neurons. Removal of all but a single whisker (single whisker experience; SWE) can trigger the strengthening of individual glutamatergic synaptic contacts onto layer 2/3 neurons only during a short window during the second and third postnatal week. At both layer 4 and putative 2/3 inputs, SWE-triggered plasticity has a discrete onset, before which it cannot be induced. SWE-synaptic strengthening is concluded at both inputs after the beginning of the third postnatal week, indicating that both types of inputs display a critical period for experience-dependent plasticity. Importantly, the timing of this critical period is both delayed and prolonged for layer 2/3-2/3 versus layer 4-2/3 excitatory synapses. Furthermore, plasticity at layer 2/3 inputs does not invoke the trafficking of calcium-permeable, GluR2-lacking AMPARs, whereas it sometimes does at layer 4 inputs. The dissociation of critical period timing and plasticity mechanisms at layer 4 and layer 2/3 synapses, despite the close apposition of these inputs along the dendrite, suggests remarkable specificity for the developmental regulation of plasticity in vivo.
These authors contributed equally to this work.Sensory information is transmitted with high fidelity across multiple synapses until it reaches the neocortex. There, individual neurons exhibit enormous variability in responses. The source of this diversity in output has been debated. Using transgenic mice expressing the green fluorescent protein coupled to the activity-dependent gene c-fos, we identified neurons with a history of elevated activity in vivo. Focusing on layer 4 to layer 2/3 connections, a site of strong excitatory drive at an initial stage of cortical processing, we find that fluorescently tagged neurons receive significantly greater excitatory and reduced inhibitory input compared with neighboring, unlabeled cells. Differential wiring of layer 2/3 neurons arises early in development and requires sensory input to be established. Stronger connection strength is not associated with evidence for recent synaptic plasticity, suggesting that these more active ensembles may not be generated over short time scales. Paired recordings show fosGFP+ neurons spike at lower stimulus thresholds than neighboring, fosGFP− neurons. These data indicate that differences in circuit construction can underlie response heterogeneity amongst neocortical neurons.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.