Trigeminohypothalamic and Reticulohypothalamic Tract Neurons in the Upper Cervical Spinal Cord and Caudal Medulla of the Rat

Sensory information that arises in orofacial organs facilitates exploratory, ingestive, and defensive behaviors that are essential to overall fitness and survival. Because the hypothalamus plays an important role in the execution of these behaviors, sensory signals conveyed by the trigeminal nerve must be available to this brain structure. Recent anatomical studies have shown that a large number of neurons in the upper cervical spinal cord and caudal medulla project directly to the hypothalamus. The goal of the present study was to identify the types of information that these neurons carry to the hypothalamus and to map the route of their ascending axonal projections. Single-unit recording and antidromic microstimulation techniques were used to identify 81 hypothalamic-projecting neurons in the caudal medulla and upper cervical (C(1)) spinal cord that exhibited trigeminal receptive fields. Of the 72 neurons whose locations were identified, 54 were in laminae I-V of the dorsal horn at the level of C(1) (n = 22) or nucleus caudalis (Vc, n = 32) and were considered trigeminohypothalamic tract (THT) neurons because these regions are within the main projection territory of trigeminal primary afferent fibers. The remaining 18 neurons were in the adjacent lateral reticular formation (LRF) and were considered reticulohypothalamic tract (RHT) neurons. The receptive fields of THT neurons were restricted to the innervation territory of the trigeminal nerve and included the tongue and lips, cornea, intracranial dura, and vibrissae. Based on their responses to mechanical stimulation of cutaneous or intraoral receptive fields, the majority of THT neurons were classified as nociceptive (38% high-threshold, HT, 42% wide-dynamic-range, WDR), but in comparison to the spinohypothalamic tract (SHT), a relatively high percentage of low-threshold (LT) neurons were also found (20%). Responses to thermal stimuli were found more commonly in WDR than in HT neurons: 75% of HT and 93% of WDR neurons responded to heat, while 16% of HT and 54% of WDR neurons responded to cold. These neurons responded primarily to noxious intensities of thermal stimulation. In contrast, all LT neurons responded to innocuous and noxious intensities of both heat and cold stimuli, a phenomenon that has not been described for other populations of mechanoreceptive LT neurons at spinal or trigeminal levels. In contrast to THT neurons, RHT neurons exhibited large and complex receptive fields, which extended over both orofacial ("trigeminal") and extracephalic ("non-trigeminal") skin areas. Their responses to stimulation of trigeminal receptive fields were greater than their responses to stimulation of non-trigeminal receptive fields, and their responses to innocuous stimuli were induced only when applied to trigeminal receptive fields. As described for SHT axons, the axons of THT and RHT neurons ascended through the contralateral brain stem to the supraoptic decussation (SOD) in the lateral hypothalamus; 57% of them then crossed the midline to reach the ipsilateral hypothalamus. Collateral projections were found in the superior colliculus, substantia nigra, red nucleus, anterior pretectal nucleus, and in the lateral, perifornical, dorsomedial, suprachiasmatic, and supraoptic hypothalamic nuclei. Additional projections (which have not been described previously for SHT neurons) were found rostral to the hypothalamus in the caudate-putamen, globus pallidus, and substantia innominata. The findings that nonnociceptive signals reach the hypothalamus primarily through the direct THT route, whereas nociceptive signals reach the hypothalamus through both the direct THT and the indirect RHT routes suggest that highly prioritized painful signals are transferred in parallel channels to ensure that this critical information reaches the hypothalamus, a brain area that regulates homeostasis and other humoral responses required for the survival of the organism.