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Article ; Online: Behavioral, neuroendocrine and physiological indicators of the circadian biology of male and female rabbits.

Aguilar-Roblero, Raúl / González-Mariscal, Gabriela

2018 Volume 51, Issue 1, Page(s) 429–453

Abstract: Adult rabbits show robust circadian rhythms of: nursing, food and water intake, hard faeces excretion, locomotion, body temperature, blood and intraocular pressure, corticosteroid secretion, and sleep. Control of several circadian rhythms involves a ... ...

Abstract	Adult rabbits show robust circadian rhythms of: nursing, food and water intake, hard faeces excretion, locomotion, body temperature, blood and intraocular pressure, corticosteroid secretion, and sleep. Control of several circadian rhythms involves a light-entrained circadian clock and a food-entrained oscillator. Nursing periodicity, however, relies on a suckling stimulation threshold. Brain structures regulating this activity include the paraventricular nucleus and preoptic area, as determined by lesions and quantification of cFOS- and PER1 clock gene-immunoreactive proteins. Melatonin synthesis in the rabbit pineal gland shows a diurnal rhythm, with highest values at night and lowest ones during the day. In kits the main zeitgeber is milk intake, which synchronizes locomotor activity, body temperature, and corticosterone secretion. Brain regions involved in these effects include the median preoptic nucleus and several olfactory structures. As models for particular human illnesses rabbits have been valuable for studying glaucoma and cardiovascular disease. Circadian variations in intraocular pressure (main risk factor for glaucoma) have been found, with highest values at night, which depend on sympathetic innervation. Rabbits fed a high fat diet develop cholesterol plaques and high blood pressure, as do humans, and such increased fat intake directly modulates cardiovascular homeostasis and circadian patterns, independently of white adipose tissue accumulation. Rabbits have also been useful to investigate the characteristics of sleep across the day and its modulation by infections, cytokines and other endogenous humoral factors. Rabbit circadian biology warrants deeper investigation of the role of the suprachiasmatic nucleus in regulating most behavioral and physiological rhythms described above.
MeSH term(s)	Animals ; Biology ; CLOCK Proteins ; Circadian Clocks ; Circadian Rhythm ; Female ; Male ; Rabbits ; Suprachiasmatic Nucleus
Chemical Substances	CLOCK Proteins (EC 2.3.1.48)
Language	English
Publishing date	2018-12-14
Publishing country	France
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	645180-9
ISSN	1460-9568 ; 0953-816X
ISSN (online)	1460-9568
ISSN	0953-816X
DOI	10.1111/ejn.14265
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Article ; Online: Bilateral lesions of the paraventricular hypothalamic nucleus disrupt nursing behavior in rabbits.

Domínguez, Miguel / Aguilar-Roblero, Raúl / González-Mariscal, Gabriela

The European journal of neuroscience

2017 Volume 46, Issue 5, Page(s) 2133–2140

Abstract: Doe rabbits nurse the litter only once a day, for around 3 min, with circa 24-h periodicity. To explore the participation of the paraventricular nucleus (PVN) in regulating this behavior, we lesioned it bilaterally with kainic acid on lactation day 7. ... ...

Abstract	Doe rabbits nurse the litter only once a day, for around 3 min, with circa 24-h periodicity. To explore the participation of the paraventricular nucleus (PVN) in regulating this behavior, we lesioned it bilaterally with kainic acid on lactation day 7. Bilateral lesions, comprising less than 50% of the total PVN volume, abolished nursing behavior (4/8 does) or severely disrupted its normal periodicity (4/8 does). In the latter case, duration of nursing bouts was normal. Body weight, food and water intake were not significantly affected by bilateral PVN lesions. Unilateral lesions of the PVN or lesions located outside this nucleus did not significantly alter nursing periodicity or any other behavioral parameter. Results indicate an important role of the PVN for (i) maintaining maternal behavior, and (ii) the periodic display of nursing across lactation in rabbits.
Language	English
Publishing date	2017-09
Publishing country	France
Document type	Journal Article
ZDB-ID	645180-9
ISSN	1460-9568 ; 0953-816X
ISSN (online)	1460-9568
ISSN	0953-816X
DOI	10.1111/ejn.13656
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Article: Altered Light Sensitivity of Circadian Clock in Shank3

Alamilla, Javier / Ramiro-Cortés, Yazmín / Mejía-López, Adriana / Chavez, José-Luis / Rivera, Dulce Olivia / Felipe, Víctor / Aguilar-Roblero, Raúl

Frontiers in neuroscience

2021 Volume 15, Page(s) 604165

Abstract: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in communication and social interaction, repetitive or stereotypical behaviors, altered sensory perception, and sleep disorders. In general, the causes of ASD ... ...

Abstract	Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in communication and social interaction, repetitive or stereotypical behaviors, altered sensory perception, and sleep disorders. In general, the causes of ASD remain unknown, but in Phelan-McDermid syndrome, it is known that the disorder is related to the haploinsufficiency of the Shank3 gene. We used an autism model with compromised glutamatergic signaling, the Shank3
Language	English
Publishing date	2021-02-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2021.604165
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Article ; Online: The anterior paraventricular thalamus modulates neuronal excitability in the suprachiasmatic nuclei of the rat.

Alamilla, Javier / Granados-Fuentes, Daniel / Aguilar-Roblero, Raúl

The European journal of neuroscience

2015 Volume 42, Issue 10, Page(s) 2833–2842

Abstract: The suprachiasmatic nucleus (SCN) in mammals is the master clock which regulates circadian rhythms. Neural activity of SCN neurons is synchronized to external light through the retinohypothalamic tract (RHT). The paraventricular thalamic nucleus (PVT) is ...

Abstract	The suprachiasmatic nucleus (SCN) in mammals is the master clock which regulates circadian rhythms. Neural activity of SCN neurons is synchronized to external light through the retinohypothalamic tract (RHT). The paraventricular thalamic nucleus (PVT) is a neural structure that receives synaptic inputs from, and projects back to, the SCN. Lesioning the anterior PVT (aPVT) modifies the behavioral phase response curve induced by short pulses of bright light. In order to study the influence of the aPVT on SCN neural activity, we addressed whether the stimulation of the aPVT can modulate the electrical response of the SCN to either retinal or RHT stimulation. Using in vitro and in vivo recordings, we found a large population of SCN neurons responsive to the stimulation of either aPVT or RHT pathways. Furthermore, we found that simultaneous stimulation of the aPVT and the RHT increased neuronal responsiveness and spontaneous firing rate (SFR) in neurons with a low basal SFR (which also have more negative membrane potentials), such as quiescent and arrhythmic neurons, but no change was observed in neurons with rhythmic firing patterns and more depolarized membrane potentials. These results suggest that inputs from the aPVT could shift the membrane potential of an SCN neuron to values closer to its firing threshold and thus contribute to integration of the response of the circadian clock to light.
MeSH term(s)	Action Potentials ; Animals ; Electric Stimulation ; Male ; Midline Thalamic Nuclei/physiology ; Neurons/physiology ; Rats ; Rats, Wistar ; Retina/physiology ; Suprachiasmatic Nucleus/physiology ; Visual Pathways/physiology
Language	English
Publishing date	2015-11
Publishing country	France
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	645180-9
ISSN	1460-9568 ; 0953-816X
ISSN (online)	1460-9568
ISSN	0953-816X
DOI	10.1111/ejn.13088
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Article ; Online: The homeostatic feeding response to fasting is under chronostatic control.

Rivera-Estrada, David / Aguilar-Roblero, Raúl / Alva-Sánchez, Claudia / Villanueva, Iván

Chronobiology international

2018 Volume 35, Issue 12, Page(s) 1680–1688

Abstract: Eating behavior is controlled by the energy needs of the organism. The need to provide a constant supply of energy to tissues is a homeostatic drive that adjusts feeding behavior to the energetic condition of the organism. On the other hand, food intake ... ...

Abstract	Eating behavior is controlled by the energy needs of the organism. The need to provide a constant supply of energy to tissues is a homeostatic drive that adjusts feeding behavior to the energetic condition of the organism. On the other hand, food intake also shows a circadian variation synchronized to the light-dark cycle and food availability. Thus, feeding is subjected to both homeostatic and circadian regulation mechanisms that determine the amount and timing of spontaneous food intake in normal conditions. In the present study we contrasted the influence of the homeostatic versus the chronostatic mechanisms on food intake in normal conditions and in response to fasting. A group of rats was subjected to food deprivation under two different temporal schemes. A constant-length 24-h food deprivation started at different times of day resulted in an increased compensatory intake. This compensatory response showed a circadian variation that resembled the rhythm of intake in non-deprived animals. When subjected to fasting periods of increasing length (24-66 h), the amount of compensatory feeding varied according to the time of day in which food was made available, being significantly less when the fast ended in the middle of the light phase or beginning of the dark phase. These oscillatory changes did not have a correlation with variations in the level of glucose or β-hydroxybutyrate in the blood. The results suggest that the mechanism of homeostatic compensation is modulated chronostatically, presumably as part of the alternation of catabolic and anabolic states matching the daily cycles of activity.
MeSH term(s)	Animals ; Circadian Rhythm/physiology ; Eating/physiology ; Energy Intake/physiology ; Fasting/physiology ; Feeding Behavior/physiology ; Food Deprivation ; Homeostasis/physiology ; Male ; Photoperiod ; Rats, Wistar
Language	English
Publishing date	2018-08-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	998996-1
ISSN	1525-6073 ; 0742-0528
ISSN (online)	1525-6073
ISSN	0742-0528
DOI	10.1080/07420528.2018.1507036
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Article ; Online: Glutamate and GABA neurotransmission from the paraventricular thalamus to the suprachiasmatic nuclei in the rat.

Alamilla, Javier / Aguilar-Roblero, Raúl

Journal of biological rhythms

2010 Volume 25, Issue 1, Page(s) 28–36

Abstract: The anterior paraventricular thalamus (aPVT) projects to the SCN, and a lesion of the aPVT leads to phase delays of circadian rhythms, instead of advances, produced by light pulses at CT23. As a first step to understanding the underlying mechanism, the ... ...

Abstract	The anterior paraventricular thalamus (aPVT) projects to the SCN, and a lesion of the aPVT leads to phase delays of circadian rhythms, instead of advances, produced by light pulses at CT23. As a first step to understanding the underlying mechanism, the authors characterized the monosynaptic responses of SCN neurons to aPVT in whole-cell recordings from brain slices in rats. Stimulation of aPVT evoked excitatory and inhibitory postsynaptic potentials in SCN neurons. Pharmacological isolation of such components indicated that the excitatory postsynaptic potential (EPSP) involves AMPA and NMDA glutamate receptors while the inhibitory postsynaptic potential (IPSP) involves GABA( A) receptors. Since the SCN comprises mostly GABA neurons, the persistence of IPSP after the blockade of glutamate receptors ruled out the possibility that GABA was released from SCN interneurons responsive to glutamate released from the paraventricular thalamus. Altogether, the present evidence demonstrates that glutamate and GABA are released in synapses between aPVT and the SCN.
MeSH term(s)	Animals ; Glutamic Acid/metabolism ; Glycine/metabolism ; Male ; Midline Thalamic Nuclei/metabolism ; Rats ; Rats, Wistar ; Suprachiasmatic Nucleus/metabolism ; Synaptic Transmission ; gamma-Aminobutyric Acid/metabolism
Chemical Substances	Glutamic Acid (3KX376GY7L) ; gamma-Aminobutyric Acid (56-12-2) ; Glycine (TE7660XO1C)
Language	English
Publishing date	2010-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	896387-3
ISSN	1552-4531 ; 0748-7304
ISSN (online)	1552-4531
ISSN	0748-7304
DOI	10.1177/0748730409357771
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Zs.A 2872: Show issues

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Article ; Online: Cerebellar spongiform degeneration is accompanied by metabolic, cellular, and motor disruption in male rats with portacaval anastomosis.

López-Cervantes, Mayra / Quintanar-Stephano, Andrés / Alcauter-Solórzano, Sarael / Hernández-Pando, Rogelio / Aguilar-Roblero, Raúl / Gasca-Martínez, Deisy / Ortíz, Juan J / Vázquez-Martínez, Olivia / Ximénez-Camilli, Cecilia / Díaz-Muñoz, Mauricio

Journal of neuroscience research

2021 Volume 99, Issue 9, Page(s) 2287–2304

Abstract: The episodes of cerebral dysfunction, known as encephalopathy, are usually coincident with liver failure. The primary metabolic marker of liver diseases is the increase in blood ammonium, which promotes neuronal damage. In the present project, we used an ...

Abstract	The episodes of cerebral dysfunction, known as encephalopathy, are usually coincident with liver failure. The primary metabolic marker of liver diseases is the increase in blood ammonium, which promotes neuronal damage. In the present project, we used an experimental model of hepatic encephalopathy in male rats by portacaval anastomosis (PCA) surgery. Sham rats had a false operation. After 13 weeks of surgery, the most distinctive finding was vacuolar/spongiform neurodegeneration exclusively in the molecular layer of the cerebellum. This cerebellar damage was further characterized by metabolic, histopathological, and behavioral approaches. The results were as follows: (a) Cellular alterations, namely loss of Purkinje cells, morphological changes, such as swelling of astrocytes and Bergmann glia, and activation of microglia; (b) Cytotoxic edema, shown by an increase in aquaporin-4 and N-acetylaspartate and a reduction in taurine and choline-derivate osmolytes; (c) Metabolic adjustments, noted by the elevation of circulating ammonium, enhanced presence of glutamine synthetase, and increase in glutamine and creatine/phosphocreatine; (d) Inflammasome activation, detected by the elevation of the marker NLRP3 and microglial activation; (e) Locomotor deficits in PCA rats as assessed by the Rotarod and open field tests. These results lead us to suggest that metabolic disturbances associated with PCA can generate the cerebellar damage that is similar to morphophysiological modifications observed in amyloidogenic disorders. In conclusion, we have characterized a distinctive cerebellar multi-disruption accompanied by high levels of ammonium and associated with spongiform neurodegeneration in a model of hepatic hypofunctioning.
MeSH term(s)	Animals ; Astrocytes/metabolism ; Astrocytes/pathology ; Cerebellum/metabolism ; Cerebellum/pathology ; Cerebellum/surgery ; Hepatic Encephalopathy/metabolism ; Hepatic Encephalopathy/pathology ; Hepatic Encephalopathy/surgery ; Locomotion/physiology ; Male ; Microglia/metabolism ; Microglia/pathology ; Neurons/metabolism ; Neurons/pathology ; Portacaval Shunt, Surgical/trends ; Purkinje Cells/metabolism ; Purkinje Cells/pathology ; Rats ; Rats, Wistar
Language	English
Publishing date	2021-06-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	195324-2
ISSN	1097-4547 ; 0360-4012
ISSN (online)	1097-4547
ISSN	0360-4012
DOI	10.1002/jnr.24853
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Article ; Online: Circadian modulation of the Cl(-) equilibrium potential in the rat suprachiasmatic nuclei.

Alamilla, Javier / Perez-Burgos, Azucena / Quinto, Daniel / Aguilar-Roblero, Raúl

BioMed research international

2014 Volume 2014, Page(s) 424982

Abstract: The suprachiasmatic nuclei (SCN) constitute a circadian clock in mammals, where γ-amino-butyric acid (GABA) neurotransmission prevails and participates in different aspects of circadian regulation. Evidence suggests that GABA has an excitatory function ... ...

Abstract	The suprachiasmatic nuclei (SCN) constitute a circadian clock in mammals, where γ-amino-butyric acid (GABA) neurotransmission prevails and participates in different aspects of circadian regulation. Evidence suggests that GABA has an excitatory function in the SCN in addition to its typical inhibitory role. To examine this possibility further, we determined the equilibrium potential of GABAergic postsynaptic currents (E(GABA)) at different times of the day and in different regions of the SCN, using either perforated or whole cell patch clamp. Our results indicate that during the day most neurons in the dorsal SCN have an E(GABA) close to -30 mV while in the ventral SCN they have an E(GABA) close to -60 mV; this difference reverses during the night, in the dorsal SCN neurons have an E(GABA) of -60 mV and in the ventral SCN they have an E(GABA) of -30 mV. The depolarized equilibrium potential can be attributed to the activity of the Na(+)-K(+)-2Cl(-) (NKCC) cotransporter since the equilibrium potential becomes more negative following addition of the NKCC blocker bumetanide. Our results suggest an excitatory role for GABA in the SCN and further indicate both time (day versus night) and regional (dorsal versus ventral) modulation of E(GABA) in the SCN.
MeSH term(s)	Animals ; Circadian Clocks/genetics ; Circadian Clocks/physiology ; Neurons/metabolism ; Patch-Clamp Techniques ; Rats ; Receptors, GABA-A/metabolism ; Solute Carrier Family 12, Member 2/metabolism ; Suprachiasmatic Nucleus/metabolism ; Synaptic Transmission/genetics ; gamma-Aminobutyric Acid/metabolism
Chemical Substances	Receptors, GABA-A ; Slc12a2 protein, rat ; Solute Carrier Family 12, Member 2 ; gamma-Aminobutyric Acid (56-12-2)
Language	English
Publishing date	2014-05-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2698540-8
ISSN	2314-6141 ; 2314-6133
ISSN (online)	2314-6141
ISSN	2314-6133
DOI	10.1155/2014/424982
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Article ; Online: Ryanodine-sensitive intracellular Ca

Aguilar-Roblero, Raúl / Quinto, Daniel / Báez-Ruíz, Adrian / Chávez, José Luis / Belin, Andrea Carmine / Díaz-Muñoz, Mauricio / Michel, Stephan / Lundkvist, Gabriella

The European journal of neuroscience

2016 Volume 44, Issue 7, Page(s) 2504–2514

Abstract: The suprachiasmatic nuclei (SCN) contain the major circadian clock responsible for generation of circadian rhythms in mammals. The time measured by the molecular circadian clock must eventually be translated into a neuronal firing rate pattern to ... ...

Abstract	The suprachiasmatic nuclei (SCN) contain the major circadian clock responsible for generation of circadian rhythms in mammals. The time measured by the molecular circadian clock must eventually be translated into a neuronal firing rate pattern to transmit a meaningful signal to other tissues and organs in the animal. Previous observations suggest that circadian modulation of ryanodine receptors (RyR) is a key element of the output pathway from the molecular circadian clock. To directly test this hypothesis, we studied the effects of RyR activation and inhibition on real time expression of PERIOD2::LUCIFERASE, intracellular calcium levels and spontaneous firing frequency in mouse SCN neurons. Furthermore, we determined whether the RyR-2 mRNA is expressed with a daily variation in SCN neurons. We provide evidence that pharmacological manipulation of RyR in mice SCN neurons alters the free [Ca
Language	English
Publishing date	2016-10
Publishing country	France
Document type	Journal Article
ZDB-ID	645180-9
ISSN	1460-9568 ; 0953-816X
ISSN (online)	1460-9568
ISSN	0953-816X
DOI	10.1111/ejn.13368
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Article ; Online: Litter size determines circadian periodicity of nursing in rabbits.

González-Mariscal, Gabriela / Lemus, Ana Celia / Vega-Gonzalez, Arturo / Aguilar-Roblero, Raúl

Chronobiology international

2013 Volume 30, Issue 5, Page(s) 711–718

Abstract: ... linear correlation (p < 0.0001; r = -0.68) was evident between time of delivery and time of nursing ...

Abstract	Nursing in rabbits occurs inside the nest with circadian periodicity. To determine the contribution of suckling stimulation in regulating such periodicity, we varied the size of the litters provided (1, 2, 4, or 6-8 pups). Nursing does, kept under a 14:10 (L:D) photoperiod, were continuously videotaped from parturition into lactation day 15. Although parturitions occurred throughout the day, a significant negative linear correlation (p < 0.0001; r = -0.68) was evident between time of delivery and time of nursing on lactation day 1, regardless of newborn number: longer intervals between these two events were seen in does delivering in the early morning than in those that gave birth late in the day. In rabbits suckling 6-8 pups, a Rayleigh analysis revealed that the population vector best describing their nursing pattern (across lactation days 1-15) had a phase angle = 58° (corresponding to solar time 0352 h and rho = 0.78; p < 0.001). In contrast, the nursing pattern of does nursing litters smaller than 6 pups did not show circadian periodicity; rather, mothers showed multiple entrances into the nest box throughout the day. Cluster analysis revealed that the main equilibrium point of intervals between suckling bouts shifted from 24 h (6-8 pups) to 6 h (4 and 2 pups) and to as low as 4 h with 1 pup. In the groups nursing 2, 4, or 6-8 pups, most nursing episodes were followed by food and water intake. Those mothers also showed self-grooming of the ventrum and nipples after nursing. The incidence of these behaviors was lower in does nursing 1 pup. In conclusion, nursing in rabbits spontaneously occurs with circadian periodicity, but it is largely modulated by a threshold of suckling stimulation.
MeSH term(s)	Animals ; Animals, Newborn ; Animals, Suckling/physiology ; Behavior, Animal ; Circadian Rhythm/physiology ; Cluster Analysis ; Female ; Lactation ; Litter Size ; Periodicity ; Photoperiod ; Rabbits ; Time Factors
Language	English
Publishing date	2013-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	998996-1
ISSN	1525-6073 ; 0742-0528
ISSN (online)	1525-6073
ISSN	0742-0528
DOI	10.3109/07420528.2013.784769
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