Damage-sensing nociceptors in the skin provide an indispensable protective function thanks to their specialized ability to detect and transmit hot temperatures that would block or inflict irreversible damage in other mammalian neurons. Here we show that the exceptional capacity of skin C-fiber nociceptors to encode noxiously hot temperatures depends on two tetrodotoxin (TTX)-resistant sodium channel α-subunits: NaV1.8 and NaV1.9. We demonstrate that NaV1.9, which is commonly considered an amplifier of subthreshold depolarizations at 20°C, undergoes a large gain of function when temperatures rise to the pain threshold. We also show that this gain of function renders NaV1.9 capable of generating action potentials with a clear inflection point and positive overshoot. In the skin, heat-resistant nociceptors appear as two distinct types with unique and possibly specialized features: one is blocked by TTX and relies on NaV1.9, and the second type is insensitive to TTX and composed of both NaV1.8 and NaV1.9. Independent of rapidly gated TTX-sensitive NaV channels that form the action potential at pain threshold, NaV1.8 is required in all heat-resistant nociceptors to encode temperatures higher than ∼46°C, whereas NaV1.9 is crucial for shaping the action potential upstroke and keeping the NaV1.8 voltage threshold within reach.

• MeSH
• akční potenciály MeSH
• buněčné linie MeSH
• kůže MeSH
• metoda terčíkového zámku MeSH
• molekulární evoluce MeSH
• myši inbrední C57BL MeSH
• napětově řízený sodíkový kanál typ 10 metabolismus   MeSH
• napětově řízený sodíkový kanál typ 11 metabolismus   MeSH
• nociceptory metabolismus   MeSH
• práh bolesti MeSH
• techniky in vitro MeSH
• vysoká teplota * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• napětově řízený sodíkový kanál typ 10 MeSH
• napětově řízený sodíkový kanál typ 11 MeSH
• Scn10a protein, mouse MeSH Prohlížeč
• Scn11a protein, mouse MeSH Prohlížeč

• MeSH
• ghrelin metabolismus   MeSH
• hypothalamus fyziologie   MeSH
• lidé MeSH
• neurony fyziologie   MeSH
• receptory ghrelinu metabolismus   MeSH
• vápníkové kanály - typ N metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• komentáře MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ghrelin MeSH
• receptory ghrelinu MeSH
• vápníkové kanály - typ N MeSH

To better understand how hippocampal place cell activity is controlled by sensory stimuli, and to further elucidate the nature of the environmental representation provided by place cells, we have made recordings in the presence of two distinct visual stimuli under standard conditions and after several manipulations of these stimuli. In line with a great deal of earlier work, we find that place cell activity is constant when repeated recordings are made in the standard conditions in which the centers of the two stimuli, a black card and a white card, are separated by 135 degrees on the wall of a cylindrical recording chamber. Rotating the two stimuli by 45 degrees causes equal rotations of place cell firing fields. Removing either card and rotating the other card also causes fields to rotate equally, showing that the two stimuli are individually salient. Increasing or decreasing the card separation (card reconfiguration) causes a topological distortion of the representation of the cylinder floor such that field centers move relative to each other. We also found that either kind of reconfiguration induces a position-independent decrease in the intensity of place cell firing. We argue that these results are not compatible with either of two previously stated views of the place cell representation; namely, a nonspatial theory in which each place cell is tuned to an arbitrarily selected subset of available stimuli or a rigid map theory. We propose that our results imply that the representation is map-like but not rigid; it is capable of undergoing stretches without altering the local arrangement of firing fields.

• MeSH
• elektrofyziologie MeSH
• hipokampus cytologie   fyziologie   MeSH
• krysa rodu Rattus MeSH
• mapování mozku * MeSH
• potkani Long-Evans MeSH
• reprodukovatelnost výsledků MeSH
• rotace MeSH
• světelná stimulace MeSH
• synapse fyziologie   MeSH
• vnímání prostoru fyziologie   MeSH
• zraková pole fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH

Changing the angular separation between two visual stimuli attached to the wall of a recording cylinder causes the firing fields of place cells to move relative to each other, as though the representation of the floor undergoes a topological distortion. The displacement of the firing field center of each cell is a vector whose length is equal to the linear displacement and whose angle indicates the direction that the field center moves in the environment. Based on the observation that neighboring fields move in similar ways, whereas widely separated fields tend to move relative to each other, we develop an empirical vector-field model that accounts for the stated effects of changing the card separation. We then go on to show that the same vector-field equation predicts additional aspects of the experimental results. In one example, we demonstrate that place cell firing fields undergo distortions of shape after the card separation is changed, as though different parts of the same field are affected by the stimulus constellation in the same fashion as fields at different locations. We conclude that the vector-field formalism reflects the organization of the place-cell representation of the environment for the current case, and through suitable modification may be very useful for describing motions of firing patterns induced by a wide variety of stimulus manipulations.

• MeSH
• akční potenciály fyziologie   MeSH
• hipokampus cytologie   fyziologie   MeSH
• interneurony fyziologie   MeSH
• krysa rodu Rattus MeSH
• mapování mozku MeSH
• modely neurologické * MeSH
• světelná stimulace MeSH
• vnímání prostoru fyziologie   MeSH
• zraková pole fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH

• Publikační typ
• časopisecké články MeSH