RESUMEN
Detailed characterization of interneuron types in primary visual cortex (V1) has greatly contributed to understanding visual perception, yet the role of chandelier cells (ChCs) in visual processing remains poorly characterized. Using viral tracing we found that V1 ChCs predominantly receive monosynaptic input from local layer 5 pyramidal cells and higher-order cortical regions. Two-photon calcium imaging and convolutional neural network modeling revealed that ChCs are visually responsive but weakly selective for stimulus content. In mice running in a virtual tunnel, ChCs respond strongly to events known to elicit arousal, including locomotion and visuomotor mismatch. Repeated exposure of the mice to the virtual tunnel was accompanied by reduced visual responses of ChCs and structural plasticity of ChC boutons and axon initial segment length. Finally, ChCs only weakly inhibited pyramidal cells. These findings suggest that ChCs provide an arousal-related signal to layer 2/3 pyramidal cells that may modulate their activity and/or gate plasticity of their axon initial segments during behaviorally relevant events.
Asunto(s)
Neuronas , Corteza Visual , Animales , Ratones , Células Piramidales , Interneuronas , Nivel de AlertaRESUMEN
Activity-dependent plasticity of the axon initial segment (AIS) endows neurons with the ability to adapt action potential output to changes in network activity. Action potential initiation at the AIS highly depends on the clustering of voltage-gated sodium channels, but the molecular mechanisms regulating their plasticity remain largely unknown. Here, we developed genetic tools to label endogenous sodium channels and their scaffolding protein, to reveal their nanoscale organization and longitudinally image AIS plasticity in hippocampal neurons in slices and primary cultures. We find that N-methyl-d-aspartate receptor activation causes both long-term synaptic depression and rapid internalization of AIS sodium channels within minutes. The clathrin-mediated endocytosis of sodium channels at the distal AIS increases the threshold for action potential generation. These data reveal a fundamental mechanism for rapid activity-dependent AIS reorganization and suggests that plasticity of intrinsic excitability shares conserved features with synaptic plasticity.
Asunto(s)
Segmento Inicial del Axón , Canales de Sodio , Potenciales de Acción , Análisis por Conglomerados , EndocitosisRESUMEN
Cortical pyramidal neurons receive thousands of synaptic inputs and transform these into action potential output. In this issue of Neuron, Lafourcade et al. (2022) demonstrate that distinct long-range projections to retrosplenial cortex pyramidal neurons are coupled to diverse modes of dendritic integration.
Asunto(s)
Dendritas , Células Piramidales , Potenciales de Acción/fisiología , Axones/fisiología , Dendritas/fisiología , Neuronas/fisiología , Células Piramidales/fisiologíaRESUMEN
The axon initial segment (AIS) is a critical microdomain for action potential initiation and implicated in the regulation of neuronal excitability during activity-dependent plasticity. While structural AIS plasticity has been suggested to fine-tune neuronal activity when network states change, whether it acts in vivo as a homeostatic regulatory mechanism in behaviorally relevant contexts remains poorly understood. Using the mouse whisker-to-barrel pathway as a model system in combination with immunofluorescence, confocal analysis and electrophysiological recordings, we observed bidirectional AIS plasticity in cortical pyramidal neurons. Furthermore, we find that structural and functional AIS remodeling occurs in distinct temporal domains: Long-term sensory deprivation elicits an AIS length increase, accompanied with an increase in neuronal excitability, while sensory enrichment results in a rapid AIS shortening, accompanied by a decrease in action potential generation. Our findings highlight a central role of the AIS in the homeostatic regulation of neuronal input-output relations.
Asunto(s)
Segmento Inicial del Axón/metabolismo , Corteza Cerebral/metabolismo , Homeostasis , Envejecimiento/fisiología , Animales , Conducta Exploratoria , Ratones Endogámicos C57BL , Plasticidad Neuronal/fisiología , Células Piramidales/fisiología , Privación Sensorial , Factores de Tiempo , Vibrisas/fisiologíaAsunto(s)
Interneuronas/citología , Interneuronas/efectos de los fármacos , Factor Inhibidor de Leucemia/farmacología , Sinapsis/efectos de los fármacos , Corteza Visual/citología , Animales , Animales Recién Nacidos , Axones/efectos de los fármacos , Factor Neurotrófico Derivado del Encéfalo/farmacología , Calcio/metabolismo , Dendritas/efectos de los fármacos , Técnicas In Vitro , Interneuronas/metabolismo , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Neuropéptido Y/genética , Neuropéptido Y/metabolismo , Técnicas de Cultivo de Órganos , Ratas , Ratas Long-Evans , Canales de Potasio Shaw/genética , Canales de Potasio Shaw/metabolismo , Sinaptotagmina II/genética , Sinaptotagmina II/metabolismo , Factores de TiempoRESUMEN
The rodent whisker-to-barrel cortex pathway is a classic model to study the effects of sensory experience and deprivation on neuronal circuit formation, not only during development but also in the adult. Decades of research have produced a vast body of evidence highlighting the fundamental role of neuronal activity (spontaneous and/or sensory-evoked) for circuit formation and function. In this context, it has become clear that neuronal adaptation and plasticity is not just a function of the neonatal brain, but persists into adulthood, especially after experience-driven modulation of network status. Mechanisms for structural remodeling of the somatodendritic or axonal domain include microscale alterations of neurites or synapses. At the same time, functional alterations at the nanoscale such as expression or activation changes of channels and receptors contribute to the modulation of intrinsic excitability or input-output relationships. However, it remains elusive how these forms of structural and functional plasticity come together to shape neuronal network formation and function. While specifically somatodendritic plasticity has been studied in great detail, the role of axonal plasticity, (e.g. at presynaptic boutons, branches or axonal microdomains), is rather poorly understood. Therefore, this review will only briefly highlight somatodendritic plasticity and instead focus on axonal plasticity. We discuss (i) the role of spontaneous and sensory-evoked plasticity during critical periods, (ii) the assembly of axonal presynaptic sites, (iii) axonal plasticity in the mature brain under baseline and sensory manipulation conditions, and finally (iv) plasticity of electrogenic axonal microdomains, namely the axon initial segment, during development and in the mature CNS.