RESUMO
How do new ideas come about? The central hypothesis presented here states that insights might happen during mental navigation and correspond to rapid plasticity at the cellular level. We highlight the differences between neocortical and hippocampal mechanisms of insight. We argue that the suddenness of insight can be related to the sudden emergence of place fields in the hippocampus. According to our hypothesis, insights are supported by a state of mind-wandering that can be tied to the process of combining knowledge pieces during sharp-wave ripples (SWRs). Our framework connects the dots between research on creativity, mental navigation, and specific synaptic plasticity mechanisms in the hippocampus.
Assuntos
Hipocampo , Neocórtex , Pensamento , Humanos , Hipocampo/fisiologia , Neocórtex/fisiologia , Plasticidade Neuronal , Pensamento/fisiologiaRESUMO
Hippocampal output influences memory formation in the neocortex, but this process is poorly understood because the precise anatomical location and the underlying cellular mechanisms remain elusive. Here, we show that perirhinal input, predominantly to sensory cortical layer 1 (L1), controls hippocampal-dependent associative learning in rodents. This process was marked by the emergence of distinct firing responses in defined subpopulations of layer 5 (L5) pyramidal neurons whose tuft dendrites receive perirhinal inputs in L1. Learning correlated with burst firing and the enhancement of dendritic excitability, and it was suppressed by disruption of dendritic activity. Furthermore, bursts, but not regular spike trains, were sufficient to retrieve learned behavior. We conclude that hippocampal information arriving at L5 tuft dendrites in neocortical L1 mediates memory formation in the neocortex.
Assuntos
Dendritos/fisiologia , Hipocampo/fisiologia , Aprendizagem/fisiologia , Neocórtex/fisiologia , Córtex Perirrinal/fisiologia , Células Piramidais/fisiologia , Animais , Hipocampo/citologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neocórtex/citologia , Optogenética , Córtex Perirrinal/citologia , Ratos WistarRESUMO
Understanding the mechanism of interactions of nanomaterials at biointerfaces is a crucial issue to develop new antimicrobial vectors. In this work, a series of water-soluble fullerene-polyglycerol sulfates (FPS) with different fullerene/polymer weight ratios and varying numbers of polyglycerol sulfate branches are synthesized, characterized, and their interactions with two distinct surfaces displaying proteins involved in target cell recognition are investigated. The combination of polyanionic branches with a solvent exposed variable hydrophobic core in FPS proves to be superior to analogs possessing only one of these features in preventing interaction of vesicular stomatitis virus coat glycoprotein (VSV-G) with baby hamster kidney cells serving as a model of host cell. Interference with L-selectin-ligand binding is dominated by the negative charge, which is studied by two assays: a competitive surface plasmon resonance (SPR)-based inhibition assay and the leukocyte cell (NALM-6) rolling on ligands under flow conditions. Due to possible intrinsic hydrophobic and electrostatic effects of synthesized compounds, pico- to nanomolar half maximal inhibitory concentrations (IC50 ) are achieved. With their highly antiviral and anti-inflammatory properties, together with good biocompatibility, FPS are promising candidates for the future development towards biomedical applications.