Representations of temperature in the spinal cord*

An animal is able to detect and interpret a wide range of temperature, while also being able to discriminate between two slightly different temperatures. Such dynamic range enables an animal not only to avoid temperature at both extremities that may cause tissue damage, but also accurately adjust its metabolism (for an endotherm) and/or behavior in response to slight ambient temperature fluctuations. How does the nervous system effectively signal this information with such a high dynamic range? External temperature is first detected by the free nerve endings in the skin, whose cell bodies are located in the dorsal root ganglia (DRG) (Fig. 1A). Over the last two decades, scientists have discovered various molecular detectors expressed by these primary sensory neurons that convert temperature information to electric impulses that can be transmitted through the nervous system. In in vitro systems, each TRP channel is featured by a distinct activation threshold temperature, such as 43 C for the heat/capsaicin-activated channel TRPV1, 25 C for the mild cold/menthol-activated channel TRPM8, 15 C for the putative cold pain channel TRPA1, etc. Upon activation, ion influx through these TRP channels leads to nerve impulses, and external temperature is detected. An important next step of the thermosensory field is to understand how electric signals generated at periphery are processed in the central nervous system, which ultimately leads to physiological/behavioral responses and generates our perception of temperature. The distinct activation thresholds of TRP channels imply a modality-specific code at periphery. Namely, dedicated “labeled lines” transmit information about an innocuous temperature or a noxious temperature. However, it is not known whether the central nervous system simply retains the modality-specific coding from the peripheral nervous system, or if the representation is transformed into a different scheme. Thus, we investigated the representations of temperature in the dorsal horn of the spinal cord, which receives inputs from primary thermosensory DRG neurons (Fig. 1A). The spinal cord is the first relay center in which thermal information is processed by a neural network before being sent to the brain (Fig. 1A). To study this representation, we developed an in vivo two-photon calcium imaging preparation, which permits simultaneous recording of thermal stimuli-evoked activities of hundreds of spinal neurons in one mouse (Fig. 1B). If each group of spinal neurons only receives inputs from a specific class of DRG neurons that expresses one type of TRP channel, these spinal neurons would simply retain the activation threshold of their DRG inputs. If so, the whole population of spinal neurons’ thresholds would cluster at a few temperature points, just like their DRG partners. Surprisingly, we found that the activation thresholds of spinal neurons are widely and rather evenly distributed in both the heat and cold ranges. No distinction between innocuous temperature-sensitive neurons and nociceptive-specific neurons was observed. Namely, the neural representation has been transformed from a modality-specific manner to a population intensity one, by which the spinal cord gradually recruits more neurons to signal increased temperature intensity. The fact that neurons have unique activation thresholds may enable the system to signal a wide spectrum of temperature with high dynamic range. We also notice that the temperature intensity-response relationships in the cold and heat ranges are different. A steep increase in the number of responsive neurons is observed when temperature rises from warmth to strong heat, whereas a more gradual increase is found in the cold range (Fig. 1C).