Neuronal basis of Hammel's model for set-point thermoregulation

Abstract

In 1965, H. T. Hammel proposed a neuronal model to explain set-point thermoregulation. His model was based on a synaptic network encompassing four different types of hypothalamic neurons: i.e., warm-sensitive and temperature-insensitive neurons and heat loss and heat production effector neurons. Although some modifications to this model are suggested, recent electrophysiological and morphological studies support many of the model's major tenets. Hypothalamic warm-sensitive neurons integrate core and peripheral thermal information. These neurons sense changes in hypothalamic temperature, and they orient their dendrites medially and laterally to receive ascending afferent input from cutaneous thermoreceptors. Temperature-insensitive neurons have a different dendritic orientation and may provide constant reference signals, which are important in determining thermoregulatory set points. In Hammel's model, temperature-sensitive and -insensitive neurons send mutually antagonistic synaptic inputs to effector neurons controlling various thermoregulatory responses. The model predicts that warm-sensitive neurons synaptically excite heat loss effector neurons and inhibit heat production effector neurons. In recent studies, one counterpart of these effector neurons may be "excitatory postsynaptic potential-driven neurons," the activity of which is dependent on synaptic excitation from nearby cells. Excitatory postsynaptic potential-driven neurons have sparse dendrites that appear to be specifically oriented, either medially or laterally, presumably to receive selective synaptic input from a discrete source. Another counterpart of effector neurons may be "silent neurons," which have extensive dendritic branches that may receive synaptic excitation from remote sources. Because some silent neurons receive synaptic inhibition from nearby warm-sensitive neurons, Hammel's model would predict that they have a role in heat production or heat retention responses.

Neurological Basis of AMP-Dependent Thermoregulation and its Relevance to Central and Peripheral Hyperthermia

“…Conversely, WSN are less represented (B20% of POA neurons) and are thought to be involved in the heat loss response. 22,23 By means of singlecell electrophysiological recording from the POA of acute hypothalamic mouse slices, we confirmed the existence of spontaneously active neurons. To identify the possible presence of TIN and WSN, we evaluated whether firing activity changed when bath temperature raised from 321C to 371C.…”

“…Several lines of evidence suggest that within the hypothalamic POA two spontaneously firing neuronal populations, namely warm-sensitive and temperature-insensitive neurons (WSN and TIN, respectively), are key effectors of hypothalamic thermoregulation. 22,23 In the rat, TIN account for B70% of POA neurons and behave like a Tb pacemaker, dictating the thermoregulatory set point. Conversely, WSN are less represented (B20% of POA neurons) and are thought to be involved in the heat loss response.…”

“…We also reason that suppression of TIN firing activity by AMP can well be the mechanisms underlying the cooling effect of the nucleotide. Indeed, TIN activity dictates the hypothalamic thermoregulatory set point, 22,23 and reduction of their firing frequency leads to a resetting to lower temperatures of their reference signal. Upon retuning the hypothalamic set point to lower temperatures, a series of autonomic responses are set into motion, including a reduction of basal metabolism and oxygen consumption.…”

“…The negative impact of AMP on firing activity of WSN, however, is at odds with the nucleotide's hypothermic effect. Indeed, according to a proposed model of hypothalamic thermoregulation, 22 reduction of WSN firing activity should promote heat retention and contrast heat loss. Thus, to better understand whether WSN inhibition by AMP in vitro had a functional correlate in vivo, we next investigated if the WSN-dependent heat loss response was impaired in AMP-challenged mice.…”

The effects of Cirazoline, an alpha-1 adrenoreceptor agonist, on the firing rates of thermally classified anterior hypothalamic neurons in rat brain slices

“…The adjustments made by thermoregulatory neurons in the POAH are responsible for raising body temperature into a hyperthermic range (Boulant, 1998). According to a current model of thermoregulation (Boulant, 2006), the contrasting responses of temperature insensitive and warm sensitive neurons are integral in mediating this shift. A decrease in the firing rate of warm sensitive neurons and concurrent increase in the firing rate of temperature insensitive neurons would inhibit heat loss responses, stimulate heat production, and elevate hypothalamic set-point temperature, as is the case during invasion of a pathogen.…”