Diversity of ancestral brainstem noradrenergic neurons across species and multiple biological factors.

The brainstem region, locus coeruleus (LC), has been remarkably conserved across vertebrates. Evolution has woven the LC into wide-ranging neural circuits that influence functions as broad as autonomic systems, the stress response, nociception, sleep, and high-level cognition among others. Given this conservation, there is a strong possibility that LC activity is inherently similar across species, and furthermore that age, sex, and brain state influence LC activity similarly across species.

Glutamatergic Projections from the Posterior Complex of the Anterior Olfactory Nucleus to the Amygdala Complexes.

Social buffering is a phenomenon where stress responses are ameliorated by an affiliative conspecific. Our previous findings suggest that the posterior complex of the anterior olfactory nucleus (AOP) is well positioned to participate in the neural mechanisms underlying social buffering. However, the lack of anatomical information prevents us from further estimating the role of the AOP.

Whole-brain afferent input mapping to functionally distinct brainstem noradrenaline cell types.

The locus coeruleus (LC) is a small region in the pons and the main source of noradrenaline (NA) to the forebrain. While traditional models suggested that all LC-NA neurons project indiscriminately throughout the brain, accumulating evidence indicates that these cells can be heterogeneous based on their anatomical connectivity and behavioral functionality and exhibit distinct coding modes. How LC-NA neuronal subpopulations are endowed with unique functional properties is unclear.

The tyrosine capsid mutations on retrograde adeno-associated virus accelerates gene transduction efficiency.

Adeno-associated virus (AAV) vector is a critical tool for gene delivery through its durable transgene expression and safety profile. Among many serotypes, AAV2-retro is typically utilized for dissecting neural circuits with its retrograde functionality. However, this vector requires a relatively long-term incubation period (over 2 weeks) to obtain enough gene expression levels presumably due to low efficiency in gene transduction.

Enhanced synchronization between prelimbic and infralimbic cortices during fear extinction learning.

The ability to extinguish aversive memories when they are no longer associated with danger is critical for balancing survival with competing adaptive demands. Previous studies demonstrated that the infralimbic cortex (IL) is essential for extinction of learned fear, while neural activity in the prelimbic cortex (PL) facilitates fear responding and is negatively correlated with the strength of extinction memories. Though these adjacent regions in the prefrontal cortex maintain mutual synaptic connectivity, it has been unclear whether PL and IL interact functionally with each other during fear extinction learning.

A dopaminergic switch for fear to safety transitions.

Overcoming aversive emotional memories requires neural systems that detect when fear responses are no longer appropriate so that they can be extinguished. The midbrain ventral tegmental area (VTA) dopamine system has been implicated in reward and more broadly in signaling when a better-than-expected outcome has occurred. This suggests that it may be important in guiding fear to safety transitions.

Modular organization of the brainstem noradrenaline system coordinates opposing learning states.

Noradrenaline modulates global brain states and diverse behaviors through what is traditionally believed to be a homogeneous cell population in the brainstem locus coeruleus (LC). However, it is unclear how LC coordinates disparate behavioral functions. We report a modular LC organization in rats, endowed with distinct neural projection patterns and coding properties for flexible specification of opposing behavioral learning states.

Projection specificity in heterogeneous locus coeruleus cell populations: implications for learning and memory.

Noradrenergic neurons in the locus coeruleus (LC) play a critical role in many functions including learning and memory. This relatively small population of cells sends widespread projections throughout the brain including to a number of regions such as the amygdala which is involved in emotional associative learning and the medial prefrontal cortex which is important for facilitating flexibility when learning rules change. LC noradrenergic cells participate in both of these functions, but it is not clear how this small population of neurons modulates these partially distinct processes.

Impairment of vesicular ATP release affects glucose metabolism and increases insulin sensitivity.

Neuroendocrine cells store ATP in secretory granules and release it along with hormones that may trigger a variety of cellular responses in a process called purinergic chemical transmission. Although the vesicular nucleotide transporter (VNUT) has been shown to be involved in vesicular storage and release of ATP, its physiological relevance in vivo is far less well understood. In Vnut knockout (Vnut(-/-)) mice, we found that the loss of functional VNUT in adrenal chromaffin granules and insulin granules in the islets of Langerhans led to several significant effects.

Correlation Between Activation of the Prelimbic Cortex, Basolateral Amygdala, and Agranular Insular Cortex During Taste Memory Formation.

Conditioned taste aversion (CTA) is a well-established learning paradigm, whereby animals associate tastes with subsequent visceral illness. The prelimbic cortex (PL) has been shown to be involved in the association of events separated by time. However, the nature of PL activity and its functional network in the whole brain during CTA learning remain unknown.

The sense of taste in the upper gastrointestinal tract.

Digestion and the absorption of food and nutrients have been considered the only functions of the gastrointestinal (GI) tract. However, recent studies suggest that taste cells in the oral cavity and taste-like cells in the GI tract share many common characteristics (taste receptors and transduction signaling). Over the last two decades, it has been revealed that the GI tract is a chemosensory organ that transfers nutrient information via GI hormone secretion (glucagon-like peptide-1, Peptide YY, oxyntomodulin, glucose-dependent insulinotropic polypeptide and others) and the activation of abdominal vagus afferents.

Reversible brain response to an intragastric load of L-lysine under L-lysine depletion in conscious rats.

L-Lysine (Lys) is an essential amino acid and plays an important role in anxiogenic behaviour in both human subjects and rodents. Previous studies have shown the existence of neural plasticity between the Lys-deficient state and the normal state. Lys deficiency causes an increase in noradrenaline release from the hypothalamus and serotonin release from the amygdala in rats.

Functional brain mapping of conscious rats during reward anticipation.

Functional magnetic resonance imaging (fMRI) in humans and non-primates has been useful to clarify the brain regions involved in the psychological process such as the reward anticipation. However, there is still no report of the fMRI study on the reward prediction in rodents. This is mainly because of the problem of anesthesia in rodent fMRI.

New therapeutic strategy for amino acid medicine: effects of dietary glutamate on gut and brain function.

The gustatory and visceral stimulation from food regulates digestion and nutrient utilization, and free glutamate (Glu) release from food is responsible for the umami taste perception that increases food palatability. The results of recent studies reveal a variety of physiological roles for Glu. For example, luminal applications of Glu into the mouth, stomach, and intestine increase the afferent nerve activities of the glossopharyngeal nerve, the gastric branch of the vagus nerve, and the celiac branch of the vagus nerve, respectively.

Evaluation of the 'liking' and 'wanting' properties of umami compound in rats.

Food reward is neurologically and psychologically divided into at least two properties; 'liking' and 'wanting'. Although umami taste enhances food palatability, the liking and wanting properties of umami taste, and the underlying neural mechanisms for these properties are not clear. Here, we compared sucrose (0, 10, 30, 120 and 480 mM) and monosodium l-glutamate (MSG; 0, 10, 30, 60 and 120 mM) solutions using a taste reactivity test to evaluate liking, and fixed/progressive-ratio operant licking tasks to evaluate wanting.

Different BOLD responses to intragastric load of L-glutamate and inosine monophosphate in conscious rats.

In this study, we compared the blood oxygen level-dependent (BOLD) signal changes between intragastric load of monosodium L-glutamate (MSG) and inosine monophosphate (IMP), which elicit the umami taste. An intragastric load of 30 mM IMP or 60 mM MSG induced a BOLD signal increase in several brain regions, including the nucleus of the solitary tract (NTS), lateral hypothalamus (LH), and insular cortex. Only MSG increased the BOLD signal in the amygdala (AMG).

Brain-gut communication via vagus nerve modulates conditioned flavor preference.

It is well known that the postingestive effect modulates subsequent food preference. We previously showed that monosodium L-glutamate (MSG) can increase flavor preference by its postingestive effect. The neural pathway involved in mediating this effect, however, remains unknown.

Blood oxygenation level-dependent response to intragastric load of corn oil emulsion in conscious rats.

The postingestive actions after intragastric or oronasal stimulation of fat have been well investigated. The blood oxygenation level-dependent (BOLD) signal changes, however, after intragastric load of corn oil emulsion have yet to be elucidated. Here, using functional magnetic resonance imaging, we investigated the BOLD signal response to gut corn oil emulsion in nonanesthetized rats.

Mechanisms of neural response to gastrointestinal nutritive stimuli: the gut-brain axis.

Background & Aims: The gut-brain axis, which transmits nutrient information from the gastrointestinal tract to the brain, is important for the detection of dietary nutrients. We used functional magnetic resonance imaging of the rat forebrain to investigate how this pathway conveys nutrient information from the gastrointestinal tract to the brain.

Methods: We investigated the contribution of the vagus nerve by comparing changes of blood oxygenation level-dependent signals between 24 control rats and 22 rats that had undergone subdiaphragmatic vagotomy.

Conditioned flavor preference learning by intragastric administration of L-glutamate in rats.

The preference for foods or fluids in rats is partly dependent on its postingestive consequences. Many studies have investigated postingestive effect of high caloric substances, such as carbohydrate or fat. In this study, we examined postingestive effect of L-glutamate at the preferable concentration using conditioned flavor preference paradigm.

Maternal approaches to pup ultrasonic vocalizations produced by a nanocrystalline silicon thermo-acoustic emitter.

When infant rodents are isolated from their mother and littermates, they cool rapidly and emit ultrasonic vocalizations (USVs). The effect of pup USVs on the mother has been investigated using models of pup USVs from ultrasonic speakers. We used a nanocrystalline silicon thermo-acoustic emitter (nc-Si emitter) to investigate mothers' responses to digitally reproduced pup USVs in mice.

Neuroprotective effect of 17beta-estradiol against N-methyl-D-aspartate-induced retinal neurotoxicity via p-ERK induction.

We investigated whether the neuroprotective effect of estrogen is mediated by the estrogen receptor (ER) and whether extracellular signal-regulated kinase (ERK) is involved in the protective effect of estrogen against N-methyl-D-aspartate (NMDA)-induced retinal neurotoxicity. Retrograde labeling of retinal ganglion cells (RGCs) showed that pretreatment with 17beta-estradiol (E2) using a silastic implant significantly attenuated the loss of RGCs induced by intravitreal injection of NMDA. Simultaneous administration of U0126, an ERK inhibitor, with NMDA completely abolished the protective effect of E2.