Separate Subpopulations Of Neurons Research Articles

Functionally Distinct Neuronal Ensembles within the Memory Engram

Memories are believed to be encoded by sparse ensembles of neurons in the brain. However, it remains unclear whether there is functional heterogeneity within individual memory engrams, i.e., if separate neuronal subpopulations encode distinct aspects of the memory and drive memory expression differently. Here, we show that contextual fear memory engrams in the mouse dentate gyrus contain functionally distinct neuronal ensembles, genetically defined by the Fos- or Npas4-dependent transcriptional pathways. The Fos-dependent ensemble promotes memory generalization and receives enhanced excitatory synaptic inputs from the medial entorhinal cortex, which we find itself also mediates generalization. The Npas4-dependent ensemble promotes memory discrimination and receives enhanced inhibitory drive from local cholecystokinin-expressing interneurons, the activity of which is required for discrimination. Our study provides causal evidence for functional heterogeneity within the memory engram and reveals synaptic and circuit mechanisms used by each ensemble to regulate the memory discrimination-generalization balance.

Substance P, tyrosine hydroxylase and serotonin terminals in the rat caudal nucleus ambiguus

Substance P (SP), tyrosine hydroxylase (TH) and serotonin inputs onto laryngeal motoneurons (LMNs) are known to exist, but the distribution of their terminals in the caudal nucleus ambiguus (NA), remains unclear. Using immunofluorescence and confocal microscopy, we assessed simultaneously the distribution of SP, TH, serotonin and synaptophysin immunoreactive (ir) terminals in the caudal NA. SP, TH and serotonin-ir varicosities were considered to represent immunoreactive synapses if, using confocal microscopy, they were co-localized with the presynaptic protein, synaptophysin. Relative to the total number of synapses, we found only a modest number of SP, TH or serotonin-ir synaptic terminals in the caudal NA. The density of SP-ir synaptic terminals was higher than that of TH-ir and serotonin-ir synaptic terminals. Our results suggest that SP, TH, and serotonin-ir inputs may play only a modest role in regulating the activity of LMN. We conclude that SP, TH and serotonin are not always co-localized in terminals forming inputs with LMN and that they arise from separate subpopulations of neurons.

Sodium deprivation and salt intake activate separate neuronal subpopulations in the nucleus of the solitary tract and the parabrachial complex

Salt intake is an established response to sodium deficiency, but the brain circuits that regulate this behavior remain poorly understood. We studied the activation of neurons in the nucleus of the solitary tract (NTS) and their efferent target nuclei in the pontine parabrachial complex (PB) in rats during sodium deprivation and after salt intake. After 8-day dietary sodium deprivation, immunoreactivity for c-Fos (a neuronal activity marker) increased markedly within the aldosterone-sensitive neurons of the NTS, which express the enzyme 11-beta-hydroxysteroid dehydrogenase type 2 (HSD2). In the PB, c-Fos labeling increased specifically within two sites that relay signals from the HSD2 neurons to the forebrain--the pre-locus coeruleus and the innermost region of the external lateral parabrachial nucleus. Then, 1-2 hours after sodium-deprived rats ingested salt (a hypertonic 3% solution of NaCl), c-Fos immunoreactivity within the HSD2 neurons was virtually eliminated, despite a large increase in c-Fos activation in the surrounding NTS (including the A2 noradrenergic neurons) and area postrema. Also after salt intake, c-Fos activation increased within pontine nuclei that relay gustatory (caudal medial PB) and viscerosensory (rostral lateral PB) information from the NTS to the forebrain. Thus, sodium deficiency and salt intake stimulate separate subpopulations of neurons in the NTS, which then transmit this information to the forebrain via largely separate relay nuclei in the PB complex. These findings offer new perspectives on the roles of sensory information from the brainstem in the regulation of sodium appetite.

Functional brainstem pathways linked to sodium deprivation and salt intake

To reveal brainstem pathways activated by sodium deprivation and salt ingestion, nuclear c-Fos immunoreactivity (a marker for neuronal activity) was examined in neurons within the nucleus of the solitary tract (NTS) and in their efferent target nuclei within the pontine parabrachial complex (PB) in rats. After 8d dietary sodium deprivation, the aldosterone-sensitive neurons in the NTS, which express 11-β-hydroxysteroid dehydrogenase type 2 (HSD2), exhibited a marked increase in c-Fos immunoreactivity. In the PB, c-Fos labeling increased specifically within the two nuclei that relay information from the HSD2 neurons to the forebrain – the pre-locus coeruleus and the inner subdivision of the external lateral nucleus. In separate groups of rats that ingested salt (3% NaCl solution) for 1 or 2h following 8d sodium-deprivation, c-Fos immunoreactivity within the HSD2 neurons was virtually eliminated, whereas a prominent increase in c-Fos labeling was found in the surrounding medial NTS (including A2 noradrenergic neurons) and area postrema. Salt ingestion also increased c-Fos labeling in PB nuclei that relay gustatory (caudal medial PB) and viscerosensory (rostral lateral PB) information from the NTS to the forebrain. Thus, sodium deficiency and salt ingestion stimulate separate subpopulations of neurons within the NTS, which transmit this information to the forebrain via largely separate nuclei in the PB. The existence of parallel, ascending signals for sodium need and salt intake offers a new perspective on the potential functions of brainstem sensory pathways in the regulation of sodium appetite.

The subfornical organ: a central target for circulating feeding signals.

The mechanisms through which circulating ghrelin relays hunger signals to the CNS are not yet fully understood. In this study, we have examined the potential role of the subfornical organ (SFO), a circumventricular structure that lacks the normal blood-brain barrier, as a CNS site in which ghrelin acts to influence the hypothalamic centers controlling food intake. We report that ghrelin increased intracellular calcium concentrations in 28% (12 of 43) of dissociated SFO neurons and that the SFO expresses mRNA for the growth hormone secretagogue receptor. Whole-cell patch recordings from SFO neurons demonstrated that in 29% (9 of 31) of neurons tested ghrelin induced a mean depolarization of 7.4 +/- 0.69 mV, accompanied by an increase in action potential frequency. Voltage-clamp recordings revealed that ghrelin activates a putative nonselective cationic conductance. Previous reports that the satiety signal amylin exerts similar excitatory effects on SFO neurons led us to examine whether these two peptides influence different subpopulations of SFO neurons. Concentration-dependent depolarizing effects of amylin were observed in 59% (28 of 47) of SFO neurons (mean depolarization, 8.32 +/- 0.60 mV). In contrast to ghrelin, voltage-clamp recordings suggest that amylin influences a voltage-dependent current activated at depolarized potentials. We tested single SFO neurons with both peptides and identified cells responsive only to ghrelin (n = 9) and only to amylin (n = 7) but no cells that responded to both peptides. These data support a role for the SFO as a center at which ghrelin and amylin may influence separate subpopulations of neurons to influence the hypothalamic regulation of feeding.

Cortical projections to the nucleus of the optic tract and dorsal terminal nucleus and to the dorsolateral pontine nucleus in macaques: a dual retrograde tracing study.

The nucleus of the optic tract and dorsal terminal nucleus of the accessory optic system (NOT-DTN) along with the dorsolateral pontine nucleus (DLPN) have been shown to play a role in controlling slow eye movements and in maintaining stable vision during head movements. Both nuclei are known to receive cortical input from striate and extrastriate cortex. To determine to what degree this cortical input arises from the same areas and potentially from the same individual neurons, we placed different retrograde tracers into the NOT-DTN and the DLPN. In the ipsilateral cortical hemisphere the two projections mainly overlapped in the posterior part of the superior temporal sulcus (STS) comprising the middle temporal area (MT), the middle superior temporal area (MST), and the visual area in the fundus of the STS (FST) and the surrounding cortex. In these areas, neurons projecting to the NOT-DTN or the DLPN were closely intermingled. Nevertheless, only 3-11% of the labeled neurons in MT and MST were double-labeled in our various cases. These results indicate that the cortical input to the NOT-DTN and DLPN arises from largely separate neuronal subpopulations in the motion sensitive areas in the posterior STS. Only a small percentage of the projection neurons bifurcate to supply both targets. These findings are discussed in relation to the optokinetic and the smooth pursuit system.

Colocalization of calbindin D-28k, calretinin, and GABA immunoreactivities in neurons of the human temporal cortex.

The calcium-binding proteins calbindin D-28k (CalB) and calretinin (CalR) have been shown to be useful markers of neuronal subpopulations located mainly in layers II-III of the neocortex of a variety of species, including human. Double labeling immunocytochemical studies of CalB, CalR, and GABA in experimental animals have shown that CalB and CalR are present in separate subpopulations of neurons. However, there are no studies of colocalization of these calcium-binding proteins and GABA in the human neocortex. The principal goal of the present work was to investigate the degree of colocalization of these substances in layers II-III of the human temporal neocortex, using a postembedding immunocytochemical method. The patterns of staining for CalB, CalR, and GABA in the human cortex were similar to those found in monkey neocortex. However, the degree of colocalization for certain combinations was different from that reported in the monkey and other experimental animals. A relatively large proportion of CalB- and CalR-immunoreactive cells (approximately 71% and 74%, respectively) were found to be immunoreactive for GABA. However, the degree of colocalization of CalB with CalR was low (between 4% and 6%). Thus, our quantitative and qualitative data suggest that these calcium-binding proteins are present in similar cortical circuits in all primates, but that in the human neocortex, there might be additional GABAergic and perhaps also non-GABAergic interneurons with unique chemical characteristics.

Responses of feline caudal hypothalamic cardiorespiratory neurons to hypoxia and hypercapnia.

Several studies have suggested that the caudal hypothalamus modulates responses to hypercapnia and hypoxia. In addition, this area of the hypothalamus contains neurons that have a sympathoexcitatory discharge. The purpose of the present study was to determine whether the basal discharge of caudal hypothalamic neurons that are stimulated by hypercapnia or hypoxia is related to cardiovascular (sympathetic discharge and/or the cardiac cycle) and/or respiratory activity (phrenic nerve discharge). Hypothalamic single unit activity, phrenic nerve activity, and cervical sympathetic nerve activity were recorded in anesthetized cats. Computer averaging techniques were used to compare temporally the discharge of hypothalamic neurons with cardiovascular and/or respiratory activity. Cardiorespiratory and hypothalamic neuronal responses to ventilation with hypoxic (10% O2/90% N2) and hypercapnic (5% CO2/95% O2) gases were determined in intact and in peripherally-chemodenervated, barodenervated cats. Thirty-two percent of hypothalamic neurons were stimulated by a hypercapnic stimulus in intact cats; of those that were stimulated by hypercapnia, all had a basal discharge related to cardiovascular and/or respiratory activity. Hypoxia significantly increased the discharge rate of 21% of hypothalamic units in intact animals; 90% of those had a cardiovascular and/or respiratory-related rhythm. Only 13% of the neurons were stimulated by both hypoxia and hypercapnia. Similar results were found in barodenervated, peripherally chemodenervated cats. Neurons excited by these stimuli in both the intact and denervated cats were found to be concentrated in the posterior hypothalamic area. The results of this study suggest that a group of caudal hypothalamic neurons contribute to the cardiorespiratory responses to hypoxia and hypercapnia, but via separate subpopulations of neurons. In addition, input from peripheral baroreceptor and chemoreceptor afferents is not required for this modulation.

Anatomical and functional compartmentalization of the subparafascicular thalamic nucleus in the rat.

The localization and the transmitter phenotype of subparafascicular thalamic nucleus (Spf) neurons projecting to the inferior colliculus (IC) and to the spinal cord (Sp) were studied by using a retrograde fluorescent double labeling technique, and a combined technique of retrograde tracing and immunohistochemistry for tyrosine hydroxylase (TH) and glutamate decarboxylase (GAD). The cell population of Spf-IC neurons was totally differentiated from that of Spf-Sp neurons which have been reported to be dopaminergic. The former were densely distributed, small to medium sized cells and localized in the central portion of the Spf, while the latter were sparsely distributed, large cells and localized in the marginal portion of the Spf. Spf-IC neurons were completely devoid of TH immunoreactivity and, instead, approximately half of them showed GAD immunoreactivity. From these findings, it is concluded that the Spf is distinctly compartmentalized by the presence at least two separate neuronal subpopulations, which are distinguishable in terms of their cell size, distribution patterns, transmitter phenotypes and trajectories.

Calbindin D-28K and parvalbumin immunoreactivity is confined to two separate neuronal subpopulations in the cat visual cortex, whereas partial coexistence is shown in the dorsal lateral geniculate nucleus

Calbindin D-28K-immunoreactive cells were localized in the supragranular layers of the striate cortex of the cat, while parvalbumin-stained cells occurred from the bottom half of layer II through layer VI, making the two distributions almost complementary. Calbindin- and parvalbumin-positive cells occurred throughout the 3 layers of the dorsal lateral geniculate nucleus (dLGN), but calbindin-immunoreactive cells outnumbered parvalbumin-positive cells. Double labeling on single sections was performed in order to determine the possible coexistence of calbindin and parvalbumin in single cells of cat visual cortex and dLGN. Calbindin and parvalbumin immunoreactivity was found in two separate neuronal populations in the visual cortex, while in the dLGN about 50% of the cells were doubly stained.

Concomitant hypotensive and antinociceptive effects of guanabenz in conscious rats: Involvement of nucleus reticularis gigantocellularis

Subcutaneous administration of guanabenz (1, 2, 5, or 8 mg/kg) in conscious Sprague-Dawley rats exerted concomitant suppressive actions on systolic pressure (tail-cuff sphygmomanometric measurement) and pain responses (hot-plate algesiometric assay) that varied both in degree (antinociception ⋙ hypotension) and response pattern. Furthermore, both depressive effects were appreciably attenuated by bilateral lesions of the nucleus reticularis gigantocellularis in the medulla oblongata. It is speculated that separate subpopulations of neurons within this reticular nucleus may be involved in the expression of hypotension and antinociception by this amino-guanidine derivative.

Hypothalamic regulation of sodium intake: relations to preoptic and tegmental function.

ARTICLESHypothalamic regulation of sodium intake: relations to preoptic and tegmental functionG WolfG WolfPublished Online:01 Dec 1967https://doi.org/10.1152/ajplegacy.1967.213.6.1433MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformationCited ByPhysiological state tunes mesolimbic signaling: Lessons from sodium appetite and inspiration from Randall R. SakaiPhysiology & Behavior, Vol. 178FoxP2 brainstem neurons project to sodium appetite regulatory sitesJournal of Chemical Neuroanatomy, Vol. 42, No. 1Parabrachial and hypothalamic interaction in sodium appetiteS. Dayawansa, S. Peckins, S. Ruch, and R. Norgren1 May 2011 | American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Vol. 300, No. 5Central regulation of sodium appetite16 January 2008 | Experimental Physiology, Vol. 93, No. 2Sodium deprivation and salt intake activate separate neuronal subpopulations in the nucleus of the solitary tract and the parabrachial complex30 July 2007 | The Journal of Comparative Neurology, Vol. 504, No. 4Aldosterone-sensitive neurons in the nucleus of the solitary tract: Efferent projections1 January 2006 | The Journal of Comparative Neurology, Vol. 497, No. 2BibliographyThe effects of preoperative ingestive events on feeding and drinking behavior following brain damage7 October 2013 | Psychobiology, Vol. 16, No. 3Animal Models of Mineralocorticoid ResistanceSteroid Hormone Receptors in Brain and PituitaryA reassessment of the brain mechanisms that control thirstNeuroscience & Biobehavioral Reviews, Vol. 8, No. 1The effects of fornix lesions on latent learning in the ratPhysiology & Behavior, Vol. 24, No. 5A Possible Role for Angiotensin in the Elicitation of Salt AppetiteInfluences of Adrenocortical Hormones on Pituitary and Brain FunctionBiology of Mineralocorticoid ReceptorsElectrolytic lesions and knife cuts in the region of the zona incerta impair sodium appetitePhysiology & Behavior, Vol. 18, No. 4The pineal gland and the development of salt intake patterns in male ratsDevelopmental Psychobiology, Vol. 9, No. 2Salt ingestion responses to diencephalic electrical stimulation in the unrestrained conscious sheepBrain Research, Vol. 70, No. 3Sodium appetite: some conceptual and methodologic aspects of a model drive systemBehavioral Biology, Vol. 10, No. 1Longitudinal analyses of daily excretory rhythms in men with tetraplegia due to cervical spinal cord transectionSpinal Cord, Vol. 10, No. 2Sex differences in the taste preference for a salt solution in the ratPhysiology & Behavior, Vol. 8, No. 2Neural mechanisms for sodium appetite: hypothalamus positive-hypothalamofugal pathways negativePhysiology & Behavior, Vol. 6, No. 4Role of Taste in Specific HungersRestoration of sodium balance in hypophysectomized rats after acute sodium deficiencyPhysiology & Behavior, Vol. 5, No. 10Neurobiology of Sodium AppetiteAnalysis of daily rhythms of adrenal function in men with quadriplegia due to spinal cord sectionSpinal Cord, Vol. 6, No. 4Relation between medial hypothalamic damage and impairments in regulation of sodium intakePhysiology & Behavior, Vol. 4, No. 1Thalamic and tegmental mechanisms for sodium intake: Anatomical and functional relations to lateral hypothalamusPhysiology & Behavior, Vol. 3, No. 6Bar pressing for food reinforcement after lesions of efferent pathways from lateral hypothalamusExperimental Neurology, Vol. 21, No. 2 More from this issue > Volume 213Issue 6December 1967Pages 1433-1438 Copyright & PermissionsCopyright © 1967 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1967.213.6.1433PubMed4864715History Published online 1 December 1967 Published in print 1 December 1967 Metrics