The trajectory of sensory pathways from the lamina terminalis to the insular and cingulate cortex: a neuroanatomical framework for the generation of thirst. Am J Physiol Regul Integr Comp Physiol 294: R1390-R1401, 2008. First published January 30, 2008 doi:10.1152/ajpregu.00869.2007The pathways involved in the emotional aspects of thirst, the arousal and affect associated with the generation of thirst and the motivation to obtain satiation, have been studied but remain poorly understood. Rats were therefore injected with the neurotropic virus pseudorabies in either the insular or cingulate cortex. After 2 days of infection, pseudorabies-positive neurons were identified within the thalamus and lamina terminalis. In a separate group of rats, the retrograde tracer cholera toxin subunit b (CTb) was used in combination with either isotonic (0.15 M NaCl) or hypertonic (0.8 M NaCl) saline (1 ml/100 g body wt ip). Rats injected with CTb in the insular cortex and stimulated with hypertonic saline had increased numbers of Fos/CTb double-positive neurons in the paraventricular, rhomboid, and reuniens thalamic nuclei, whereas those rats injected with CTb in the cingulate cortex and challenged with hypertonic saline had increased numbers of Fos/CTb double-positive neurons in the medial part of the mediodorsal, interanteromedial, anteromedial, and ventrolateral part of the laterodorsal thalamic nuclei. Rats injected with CTb in the dorsal midline of the thalamus and challenged with hypertonic saline had increased numbers of Fos/CTb double-positive neurons within the organum vasculosum of the lamina terminalis (OVLT), median preoptic nucleus, and insular cortex but not the subfornical organ. A small proportion of the CTb-positive neurons in the OVLT were immunopositive for transient receptor potential vanilloid 1, a putative osmoresponsive membrane protein. These results identify functional thalamocortical pathways involved in relaying osmotic signals to the insular and cingulate cortex and may provide a neuroanatomical framework for the emotional aspects of thirst. organum vasculosum; subfornical organ; hypertonic saline; pseudorabies; cholera toxin THE LAMINA TERMINALIS, which contains the organum vasculosum of the lamina terminalis (OVLT), subfornical organ, and median preoptic nucleus, relays osmotic and endocrine signals to the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus to regulate vasopressin secretion (36,38,44,45,55,64,69,70). Putative osmoresponsive membrane proteins expressed within the lamina terminalis, transient receptor potential vanilloid (TRPV) 1 and TRPV4, are important for osmoreception and subsequent vasopressin secretion following hyperosmotic stimulation (12,30,31,59). The lamina terminalis contains efferent projections to regions other than the PVN and SON (34,39,46), including the lateral hypothalamus (4), periaqueductal gray (33), and thalamus (10, 50), suggesting that the lamina terminalis may be important for physiological responses to osmotic signals other than neuroendocr...