Ascending projections from the caudal visceral nucleus of the solitary tract to brain regions involved in food intake and energy expenditure

“…GLP-1 signaling pathways are implicated in the central control of food intake, glucose homeostasis, and HPA axis and autonomic responses to stress (Holst, 2007; Imeryuz et al., 1997; Kinzig et al., 2003; Nakade et al., 2007; Rinaman, 1999a; Sandoval et al., 2008; Tang-Christensen et al., 2001;…”

“…are implicated in the central control of food intake, glucose homeostasis, and HPA axis and autonomic responses to stress (Holst, 2007; Imeryuz et al., 1997; Kinzig et al., 2003; Nakade et al., 2007; Rinaman, 1999a; Sandoval et al., 2008; Tang-Christensen et al., 2001; Turton et al., 1996).”

“H129 undergoes anterograde transneuronal transport in cebus monkeys after inoculation of primary motor cortex (Kelly and Strick, 2003; Zemanick et al., 1991) and in mice after inoculation of tooth pulp (Barnett et al., 1995) or the vitreous body of the eye (Sun et al., 1996).”

“…description of the central projections of NST neurons effectively reveals most CNS recipients of viscerosensory information (Bailey et al., 2006; Horst et al., 1989; Horst and Streefland, 1994; Ricardo and Koh, 1978), albeit without identifying the central targets of organ-specific sensory signals.”

“The PBN has at least 12 distinct subnuclei, some of which project to central targets that do not receive direct input from the NST (Fulwiler and Saper, 1984;Herbert et al., 1990;Moga et al., 1990;Saper and Loewy, 1980).”

“(Gerfen and Sawchenko, 1984), into the caudal visceral NST. Coronal brain sections (35 µm thick) were cut from the caudal medulla through the rostral extent of the corpus callosum, and a one-in-six series was processed for immunoperoxidase localization of PhAL.”

“…NST neurons that project to the hypothalamus and limbic forebrain are NA neurons of the overlapping A2/C2 cell groups (Sawchenko and Swanson, 1981; Sawchenko and Swanson, 1982a; Sawchenko and Swanson, 1982b), with remaining projection neurons primarily comprising smaller and separate populations…”

“…NST neurons that project to the hypothalamus and limbic forebrain are NA neurons of the overlapping A2/C2 cell groups (Sawchenko and Swanson, 1981; Sawchenko and Swanson, 1982a; Sawchenko and Swanson, 1982b), with remaining projection neurons primarily comprising smaller and separate populations…”

“The PBN has at least 12 distinct subnuclei, some of which project to central targets that do not receive direct input from the NST (Fulwiler and Saper, 1984;Herbert et al., 1990;Moga et al., 1990;Saper and Loewy, 1980).”

“The PBN has at least 12 distinct subnuclei, some of which project to central targets that do not receive direct input from the NST (Fulwiler and Saper, 1984;Herbert et al., 1990;Moga et al., 1990;Saper and Loewy, 1980).”

“The direct inputs from NST to ACB (ventral striatum) are of particular interest, given the prominent role of this limbic brain region in appetitive motivation (Kelley, 2004;Zheng et al., 2007).”

“A strong topography is evident in the terminal arborizations of primary visceral afferents, with inputs from the gut terminating within the caudal medial NST (Altschuler et al., 1989; Shapiro and Miselis, 1985).”

“Cechetto and Saper reported a similar topographic pattern of visceral sensory responses in rats, involving regions of insular cortex that corresponded to viscerotopically organized inputs from the thalamus (Cechetto and Saper, 1987).”

“As a case in point, experimental evidence supports the view that central prolactin releasing peptide (PrRP) signaling is involved in stress-related hypophagia (Lawrence et al., 2000; Lawrence et al., 2002; Lawrence et al., 2004), and PrRP is co-expressed by a subset of NA neurons within the NST that project to hypotha…”

“…from hypothalamus to caudal brainstem provide critical control over the initiation and termination of food intake and feeding-related autonomic adjustments (Berthoud, 2002; Berthoud et al., 2006; Coll et al., 2007; Smith, 2000; Smith, 2003; Woods and D'Alessio, 2008; Zheng et al., 2005).”

“The large majority of NST neurons that project to the hypothalamus and limbic forebrain are NA neurons of the overlapping A2/C2 cell groups (Sawchenko and Swanson, 1981; Sawchenko and Swanson, 1982a; Sawchenko and Swanson, 1982b), with remaining projection neurons primarily comprising smaller and…”

“A strong topography is evident in the terminal arborizations of primary visceral afferents, with inputs from the gut terminating within the caudal medial NST (Altschuler et al., 1989; Shapiro and Miselis, 1985).”

“Interestingly, PhALlabeled fibers tend to avoid the ventromedial hypothalamic nucleus (VMH), which has classically demonstrated roles in the central control of feeding and metabolism (King, 2006;Plata-Salaman, 1998).”

“…IH -PA Author M anuscript N IH -PA Author M anuscript information regarding the involvement of particular diencephalic and limbic forebrain regions in the central neural control of food intake and energy expenditure (Berthoud, 2002; Berthoud, 2008; Broberger, 2005; Woods and D'Alessio, 2008).”

“…pathways are implicated in the central control of food intake, glucose homeostasis, and HPA axis and autonomic responses to stress (Holst, 2007; Imeryuz et al., 1997; Kinzig et al., 2003; Nakade et al., 2007; Rinaman, 1999a; Sandoval et al., 2008; Tang-Christensen et al., 2001; Turton et al.,…”

“The PBN has at least 12 distinct subnuclei, some of which project to central targets that do not receive direct input from the NST (Fulwiler and Saper, 1984;Herbert et al., 1990;Moga et al., 1990;Saper and Loewy, 1980).”

“GLP-1 modulates the activity of hypocretin/orexin-positive (but not melaninconcentrating hormone-positive) neurons within the LHA (Acuna-Goycolea and Pol, 2004), implicating GLP-1 signaling in behavioral arousal and reward-based feeding (Borgland et al., 2009; Cason et al., 2010 (in press)).”

“11) and adjacent dorsal reticular formation (Jin et al., 1988;Larsen et al., Brain Res.”

“…are implicated in the central control of food intake, glucose homeostasis, and HPA axis and autonomic responses to stress (Holst, 2007; Imeryuz et al., 1997; Kinzig et al., 2003; Nakade et al., 2007; Rinaman, 1999a; Sandoval et al., 2008; Tang-Christensen et al., 2001; Turton et al., 1996).”

“Since most neural pathways conveying interoceptive signals from body to brain involve a synaptic relay within the NST, a description of the central projections of NST neurons effectively reveals most CNS recipients of viscerosensory information (Bailey et al., 2006; Horst et al., 1989; Horst and Streefland, 1994; Rica…”

“information regarding the involvement of particular diencephalic and limbic forebrain regions in the central neural control of food intake and energy expenditure (Berthoud, 2002; Berthoud, 2008; Broberger, 2005; Woods and D'Alessio, 2008).”

“Although glucoprivic feeding induced by systemic 2-deoxyglucose is abolished in rats after bilateral destruction of NA inputs to the PVH (Ritter et al., 2001), it is unclear whether the same ascending pathways are important for the control of food intake under non-stressful, physiological conditions.”

“The direct inputs from NST to ACB (ventral striatum) are of particular interest, given the prominent role of this limbic brain region in appetitive motivation (Kelley, 2004;Zheng et al., 2007).”

“…that project to the hypothalamus are activated by interoceptive stimuli that stimulate the HPA stress axis and also inhibit food intake in rats (Rinaman, 1999b), and central antagonism of GLP-1 receptors is sufficient to attenuate the hypophagic effect of lithium chloride (Rinaman, 1999a;…”

“Stornetta RL, Sevigny CP, Guyenet PG. Vesicular glutamate transporter DNPI/VGLUT2 mRNA is present in C1 and several other groups of brainstem catecholaminergic neurons.”

“H129 undergoes anterograde transneuronal transport in cebus monkeys after inoculation of primary motor cortex (Kelly and Strick, 2003; Zemanick et al., 1991) and in mice after inoculation of tooth pulp (Barnett et al.”

“GLP-1 modulates the activity of hypocretin/orexin-positive (but not melaninconcentrating hormone-positive) neurons within the LHA (Acuna-Goycolea and Pol, 2004), implicating GLP-1 signaling in behavioral arousal and reward-based feeding (Borgland et al., 2009; Cason et al., 2010 (in press)).”

“we turned to a novel transneuronal anterograde tracer, the H129 strain of herpes simplex virus-1 (Dix et al., 1983).”

“In addition to receiving direct inputs from the caudal medial NST, the basal forebrain cholinergic corticopetal system also receives inputs relayed via the nucleus paragigantocellularis and LC (Bernston et al., 1998; Berntson et al., 2003).”

“…are implicated in the central control of food intake, glucose homeostasis, and HPA axis and autonomic responses to stress (Holst, 2007; Imeryuz et al., 1997; Kinzig et al., 2003; Nakade et al., 2007; Rinaman, 1999a; Sandoval et al., 2008; Tang-Christensen et al., 2001; Turton et al., 1996).”

“As a case in point, experimental evidence supports the view that central prolactin releasing peptide (PrRP) signaling is involved in stress-related hypophagia (Lawrence et al., 2000; Lawrence et al., 2002; Lawrence et al., 2004), and PrRP is co-expressed by a subset of NA neurons within the NST that project to hypotha…”

“Despite a long scientific history supporting the involvement of central NA signaling in the central control of food intake and energy expenditure (Leibowitz et al., 1988; Ritter et al., 1975), it still is not clear whether or how NA inputs to the hypothalamus are involved in day-to-day regulation of energy balance.”

“12) (Alvarez et al., 1996; Merchenthaler et al., 1999).”

“…are implicated in the central control of food intake, glucose homeostasis, and HPA axis and autonomic responses to stress (Holst, 2007; Imeryuz et al., 1997; Kinzig et al., 2003; Nakade et al., 2007; Rinaman, 1999a; Sandoval et al., 2008; Tang-Christensen et al., 2001; Turton et al., 1996).”

“In addition to receiving direct inputs from the caudal medial NST, the basal forebrain cholinergic corticopetal system also receives inputs relayed via the nucleus paragigantocellularis and LC (Bernston et al., 1998; Berntson et al., 2003).”

“…from hypothalamus to caudal brainstem provide critical control over the initiation and termination of food intake and feeding-related autonomic adjustments (Berthoud, 2002; Berthoud et al., 2006; Coll et al., 2007; Smith, 2000; Smith, 2003; Woods and D'Alessio, 2008; Zheng et al., 2005).”

“…to the hypothalamus are activated by interoceptive stimuli that stimulate the HPA stress axis and also inhibit food intake in rats (Rinaman, 1999b), and central antagonism of GLP-1 receptors is sufficient to attenuate the hypophagic effect of lithium chloride (Rinaman, 1999a; Seeley et al., 2000).”

“…PVH are critical for the ability of systemic cholecystokinin-8 (CCK), lipopolysaccharide, lithium chloride, or yohimbine to activate Fos expression in PVH neurons, including CRH-positive neurons (Banihashemi and Rinaman, 2006; Bienkowski and Rinaman, 2008; Rinaman, 2003b; Rinaman and Dzmura, 2007).”

“…(NA) neurons within the caudal visceral NST and closely adjacent reticular formation (Larsen et al., 1997; Merchenthaler et al., 1999; Rinaman, 1999b; Vrang et al., 2007), thereby providing a clear view of ascending pathways arising from this small group of phenotypically distinct neurons.”

“Medullary NA inputs to the hypothalamus provide critical control over the activity of stress-responsive corticotropin releasing hormone (CRH)-containing neurons within the PVH, at the apex of the HPA axis (Al-Damluji, 1988; Alonso et al., 1986; Banihashemi and Rinaman, 2006; Bienkowski and Rinaman, 2008; Gaillet et al…”

“HSD2-positive NST neurons are implicated in the central control of sodium appetite (Geerling et al., 2006a;Geerling and Loewy, 2007), and appear to project to a discrete subset of the brain regions that receive input from NA and GLP-1-positive NST neurons (Geerling and Loewy, 2006).”

“Since most neural pathways conveying interoceptive signals from body to brain involve a synaptic relay within the NST, a description of the central projections of NST neurons effectively reveals most CNS recipients of viscerosensory information (Bailey et al., 2006; Horst et al., 1989; Horst and Streefland, 1994; Rica…”

“As a case in point, experimental evidence supports the view that central prolactin releasing peptide (PrRP) signaling is involved in stress-related hypophagia (Lawrence et al., 2000; Lawrence et al., 2002; Lawrence et al., 2004), and PrRP is co-expressed by a subset of NA neurons within the NST that project to hypotha…”

“Indeed, the entire forebrain appears to be unnecessary for CCK-induced hypophagia (Grill and Smith, 1988).”

“Ample evidence supports the view that descending projections from hypothalamus to caudal brainstem provide critical control over the initiation and termination of food intake and feeding-related autonomic adjustments (Berthoud, 2002; Berthoud et al., 2006; Coll et al., 2007; Smith, 2000; Smith, 2003; Woods and D'Aless…”

“Ample evidence supports the view that descending projections from hypothalamus to caudal brainstem provide critical control over the initiation and termination of food intake and feeding-related autonomic adjustments (Berthoud, 2002; Berthoud et al., 2006; Coll et al., 2007; Smith, 2000; Smith, 2003; Woods and D'Aless…”

“Indeed, fewer than 20% of NA axon terminals within the ventrolateral BST form synaptic contacts (Phelix et al., 1992), and a hallmark of NA terminals within the medial PVH, ventrolateral BST, and other forebrain regions that receive dense inputs from the A2 region of caudal NST is the predominance of axonal varicositi…”

“GLP-1 modulates the activity of hypocretin/orexin-positive (but not melaninconcentrating hormone-positive) neurons within the LHA (Acuna-Goycolea and Pol, 2004), implicating GLP-1 signaling in behavioral arousal and reward-based feeding (Borgland et al.”

“Medullary NA inputs to the hypothalamus provide critical control over the activity of stress-responsive corticotropin releasing hormone (CRH)-containing neurons within the PVH, at the apex of the HPA axis (Al-Damluji, 1988; Alonso et al., 1986; Banihashemi and Rinaman, 2006; Bienkowski and Rinaman, 2008; Gaillet et al…”

“GLP-1-positive neurons are not adrenergic, but co-express β inhibin 1, somatostatin, and met-enkephalin (Sawchenko et al., 1990).”

“…control over the activity of stress-responsive corticotropin releasing hormone (CRH)-containing neurons within the PVH, at the apex of the HPA axis (Al-Damluji, 1988; Alonso et al., 1986; Banihashemi and Rinaman, 2006; Bienkowski and Rinaman, 2008; Gaillet et al., 1991; Kiss and Aguilera, 1992;…”

“…that project to the hypothalamus are activated by interoceptive stimuli that stimulate the HPA stress axis and also inhibit food intake in rats (Rinaman, 1999b), and central antagonism of GLP-1 receptors is sufficient to attenuate the hypophagic effect of lithium chloride (Rinaman, 1999a;…”

“5) (for more detail, see (Karimnamazi et al., 2002)).”

“As a case in point, experimental evidence supports the view that central prolactin releasing peptide (PrRP) signaling is involved in stress-related hypophagia (Lawrence et al., 2000; Lawrence et al., 2002; Lawrence et al., 2004), and PrRP is co-expressed by a subset of NA neurons within the NST that project to hypotha…”

“…also are compared to the distribution of CNS neurons that become infected/labeled after inoculating the ventral stomach wall with H129, a neurotropic α-herpesvirus virus that transneuronally infects synaptically-linked chains of neurons in the anterograde direction (Rinaman and Schwartz, 2004).”

“Medullary NA inputs to the hypothalamus provide critical control over the activity of stress-responsive corticotropin releasing hormone (CRH)-containing neurons within the PVH, at the apex of the HPA axis (Al-Damluji, 1988; Alonso et al., 1986; Banihashemi and Rinaman, 2006; Bienkowski and Rinaman, 2008; Gaillet et al…”

“13A), PVT, and dorsal and ventral BST (Larsen et al., 1997;Merchenthaler et al., 1999;Rinaman, 1999b;Sarkar et al., 2003) (Fig.”

“HSD2-positive NST neurons are implicated in the central control of sodium appetite (Geerling et al., 2006a;Geerling and Loewy, 2007), and appear to project to a discrete subset of the brain regions that receive input from NA and GLP-1-positive NST neurons (Geerling and Loewy, 2006).”

“, 1991) and in mice after inoculation of tooth pulp (Barnett et al., 1995) or the vitreous body of the eye (Sun et al.”

“…(Phelix et al., 1992), and a hallmark of NA terminals within the medial PVH, ventrolateral BST, and other forebrain regions that receive dense inputs from the A2 region of caudal NST is the predominance of axonal varicosities that do not form synaptic contacts (Balcita-Pedicino and Rinaman, 2007).”

“…terminals robustly innervate corticotropin releasing hormone (CRH)-positive neurons within the hypothalamic PVH (Sarkar et al., 2003), the apex of the HPA stress axis, as well as oxytocin (but not vasopressin) -positive neurons within the PVH and supraoptic nucleus (Rinaman and Rothe, 2002).”

“, 1995) or the vitreous body of the eye (Sun et al., 1996).”

“…corticotropin releasing hormone (CRH)-containing neurons within the PVH, at the apex of the HPA axis (Al-Damluji, 1988; Alonso et al., 1986; Banihashemi and Rinaman, 2006; Bienkowski and Rinaman, 2008; Gaillet et al., 1991; Kiss and Aguilera, 1992; Liposits et al., 1986; Rinaman, 2007).”

“…PVH are critical for the ability of systemic cholecystokinin-8 (CCK), lipopolysaccharide, lithium chloride, or yohimbine to activate Fos expression in PVH neurons, including CRH-positive neurons (Banihashemi and Rinaman, 2006; Bienkowski and Rinaman, 2008; Rinaman, 2003b; Rinaman and Dzmura, 2007).”

“…corticotropin releasing hormone (CRH)-containing neurons within the PVH, at the apex of the HPA axis (Al-Damluji, 1988; Alonso et al., 1986; Banihashemi and Rinaman, 2006; Bienkowski and Rinaman, 2008; Gaillet et al., 1991; Kiss and Aguilera, 1992; Liposits et al., 1986; Rinaman, 2007).”

“…that central prolactin releasing peptide (PrRP) signaling is involved in stress-related hypophagia (Lawrence et al., 2000; Lawrence et al., 2002; Lawrence et al., 2004), and PrRP is co-expressed by a subset of NA neurons within the NST that project to hypothalamic and limbic forebrain targets,…”

“HSD2-positive NST neurons are implicated in the central control of sodium appetite (Geerling et al., 2006a;Geerling and Loewy, 2007), and appear to project to a discrete subset of the brain regions that receive input from NA and GLP-1-positive NST neurons (Geerling and Loewy, 2006).”

“…PVH are critical for the ability of systemic cholecystokinin-8 (CCK), lipopolysaccharide, lithium chloride, or yohimbine to activate Fos expression in PVH neurons, including CRH-positive neurons (Banihashemi and Rinaman, 2006; Bienkowski and Rinaman, 2008; Rinaman, 2003b; Rinaman and Dzmura, 2007).”

“…PVH are critical for the ability of systemic cholecystokinin-8 (CCK), lipopolysaccharide, lithium chloride, or yohimbine to activate Fos expression in PVH neurons, including CRH-positive neurons (Banihashemi and Rinaman, 2006; Bienkowski and Rinaman, 2008; Rinaman, 2003b; Rinaman and Dzmura, 2007).”

“Despite a long scientific history supporting the involvement of central NA signaling in the central control of food intake and energy expenditure (Leibowitz et al., 1988; Ritter et al., 1975), it still is not clear whether or how NA inputs to the hypothalamus are involved in day-to-day regulation of energy balance.”

“Conversely, the influence of these ascending projections in regulating food intake is less firmly established (Luckman and Lawrence, 2003; Renner et al., 2010).”

“It seems curious that relatively little transneuronal H129 infection was observed within the ventrolateral BST, a forebrain region that receives particularly dense NA (Banihashemi and Rinaman, 2006; Myers et al., 2005) and GLP-1 inputs from the caudal NST (Fig.”

“…are implicated in the central control of food intake, glucose homeostasis, and HPA axis and autonomic responses to stress (Holst, 2007; Imeryuz et al., 1997; Kinzig et al., 2003; Nakade et al., 2007; Rinaman, 1999a; Sandoval et al., 2008; Tang-Christensen et al., 2001; Turton et al., 1996).”

“, 1991), VMH neurons are activated by gastric distension via a vagal sensory pathway (Sun et al., 2006).”

“However, similar to neurons within the PVH and LHA (Jeanningros, 1984;Jin et al., 1993;Ueta et al., 1991), VMH neurons are activated by gastric distension via a vagal sensory pathway (Sun et al.”

“Food intake is inhibited in rats after lateral or third ventricular administration of synthetic GLP-1 or agonist, or after microinjection of GLP-1 or agonist into the PVH, LHA, DMH, or VMH (Donahey et al., 1998; Schick et al., 2003).”

“, 2004), and PrRP is co-expressed by a subset of NA neurons within the NST that project to hypothalamic and limbic forebrain targets, including the PVH, paraventricular thalamic nucleus, DMH, medial preoptic area, periVMH, and BST (Renner et al., 2010; Yano et al., 2001).”

“, 2004), and PrRP is co-expressed by a subset of NA neurons within the NST that project to hypothalamic and limbic forebrain targets, including the PVH, paraventricular thalamic nucleus, DMH, medial preoptic area, periVMH, and BST (Renner et al., 2010; Yano et al., 2001).”

“…(Phelix et al., 1992), and a hallmark of NA terminals within the medial PVH, ventrolateral BST, and other forebrain regions that receive dense inputs from the A2 region of caudal NST is the predominance of axonal varicosities that do not form synaptic contacts (Balcita-Pedicino and Rinaman, 2007).”

“NA terminals also synapse directly onto thyrotropin releasinghormone-positive neurons within the PVH (Füzesi et al., 2009), implicating NA pathways from the NST in metabolic responses to visceral stimuli.”

“Interestingly, PhALlabeled fibers tend to avoid the ventromedial hypothalamic nucleus (VMH), which has classically demonstrated roles in the central control of feeding and metabolism (King, 2006;Plata-Salaman, 1998).”

“…NST to higher brain regions are probably mostly glutamatergic, based on extensive colocalization of tyrosine hydroxylase (the rate-limiting enzyme for catecholamine 1The rostral gustatory NST gives rise to a largely distinct and more limited set of efferent projections (Norgren et al., 2003).”

“Stimulants increased insulin levels in a PCP-induced model of schizophrenia (179) Glucagon-like peptide-1 (GLP-1) (180) Small intestine Oral taste buds Some anorexic effects appear to be exerted at the level of the mesolimbic reward system (181) Exendin, a GLP-1 receptor agonist modulates behavioural activation by amp…”

“…(DMV) to evoke vago-vagal reflexes, to other hindbrain sites to control sympathetic outflow, and to more rostral sites to control behavior, autonomic outflow, and neuroendocrine responses (Ghosal et al., 2017; Grill and Hayes, 2012; Rinaman, 2010; Trapp and Cork, 2015; Travagli and Anselmi, 2016).”