Control of protein intake is essential for numerous biological processes as several amino acids cannot be synthesized de novo , however, its neurobiological substrates are still poorly understood. In the present study, we combined in vivo fiber photometry with nutrient-conditioned flavor in a rat model of protein appetite to record neuronal activity in the ventral tegmental area (VTA), a central brain region for the control of food-related processes. In adult male rats, protein restriction increased preference for casein (protein) over maltodextrin (carbohydrate). Moreover, protein consumption was associated with a greater VTA response relative to carbohydrate. After initial nutrient preference, a switch from a normal balanced diet to protein restriction induced rapid development of protein preference but required extensive exposure to macronutrient solutions to induce greater VTA responses to casein. Furthermore, prior protein restriction induced long-lasting food preference and VTA responses. This study ...

Forrest Gump or Matrix? Preference-based decisions are subjective and entail self-reflection. However, these self-related features are unaccounted for by known neural mechanisms of valuation and choice. Self-related processes have been linked to a basic interoceptive biological mechanism, the neural monitoring of heartbeats, in particular in ventromedial prefrontal cortex (vmPFC), a region also involved in value encoding. We thus hypothesized a functional coupling between the neural monitoring of heartbeats and the precision of value encoding in vmPFC. Human participants of both sexes were presented with pairs of movie titles. They indicated either which movie they preferred, or performed a control objective visual discrimination that did not require self-reflection. Using magnetoencephalography, we measured heartbeat-evoked responses (HERs) before option presentation, and confirmed that HERs in vmPFC were larger when preparing to the subjective, self-related task. We retrieved the expected cortical value ...

In humans, impaired response inhibition is characteristic of a wide range of psychiatric diseases and of normal aging. It is hypothesised that the right inferior frontal cortex plays a key role by inhibiting the motor cortex via the basal ganglia. The electroencephalography-derived beta rhythm (15-29 Hz) is thought to reflect communication within this network, with increased right frontal beta power often observed prior to successful response inhibition. Recent literature suggests that averaging spectral power obscures the transient, burst-like nature of beta activity. There is evidence that the rate of beta bursts following a Stop signal is higher when a motor response is successfully inhibited. However, other characteristics of beta burst events, and their topographical properties, have not yet been examined. Here, we used a large human (male and female) electroencephalography Stop Signal Task dataset (n=218) to examine averaged normalised beta power, beta burst rate and beta burst ‘volume’ (which we def...

Understanding speech in background noise is a difficult task. The tracking of speech rhythms such as the rate of syllables and words by cortical activity has emerged as a key neural mechanism for speech-in-noise comprehension. In particular, recent investigations have used transcranial alternating current stimulation (tACS) with the envelope of a speech signal to influence the cortical speech tracking, demonstrating that this type of stimulation modulates comprehension and therefore evidencing a functional role of the cortical tracking in speech processing. Cortical activity has been found to track the rhythms of a background speaker as well, but the functional significance of this neural response remains unclear. Here we employ a speech-comprehension task with a target speaker in the presence of a distractor voice to show that tACS with the speech envelope of the target voice as well as tACS with the envelope of the distractor speaker both modulate the comprehension of the target speech. Because the envel...

Alzheimer’s disease (AD) is an incurable neurodegenerative disorder and a major cause of dementia. Some of the hallmarks of AD include presence of amyloid plaques in brain parenchyma, calcium dysregulation within individual neurons, and neuroinflammation. A promising therapeutic would reverse or stymie these pathophysiologies in an animal model of AD. We tested the effect of NB-02, previously known as DA-9803, a novel multimodal therapeutic, on amyloid deposition, neuronal calcium regulation and neuroinflammation in 8-10 month old APP/PS1 mice, an animal model of AD. In vivo multiphoton microscopy revealed that 2 month-long administration of NB-02 halted amyloid plaque deposition and cleared amyloid in the cortex. Post-mortem analysis verified NB-02-dependent decrease in plaque deposition in the cortex as well as hippocampus. Furthermore, drug treatment reversed neuronal calcium elevations, thus restoring neuronal function. Finally, NB-02 restored spine density and transformed the morphology of astrocytes ...

Insulin-like growth factor-I (IGF-I) signalling plays a key role in learning and memory processes. While the effects of IGF-I on neurons have been studied extensively, the involvement of astrocytes in IGF-I signalling and the consequences on synaptic plasticity and animal behavior remain unknown. We have found that IGF-I induces long-term potentiation (LTP, here called LTPIGFI) of the postsynaptic potentials that is caused by a long-term depression (LTD) of inhibitory synaptic transmission in mice. We have demonstrated that this long-lasting decrease in the inhibitory transmission is evoked by astrocytic activation through its IGF-IRs. We show that LTPIGFI not only increases the output of pyramidal neurons, but also favours the N-methyl-D-aspartate (NMDAR) dependent LTP, resulting in the crucial information processing at the Barrel cortex since specific deletion of IGF-IR in cortical astrocytes (IGF-IR-/-) impairs the whisker discrimination task. Our work reveals a novel mechanism and functional consequenc...

The Abelson-helper integration site 1 ( AHI1 ) gene encodes for a ciliary transition zone localizing protein that when mutated causes the human ciliopathy, Joubert syndrome. We prepared and examined neuronal cultures derived from male and female embryonic Ahi1 +/+ and Ahi1 –/– mice (littermates) and found that the distribution of ciliary melanin-concentrating hormone receptor-1 (MchR1) was significantly reduced in Ahi1 –/– neurons; however, the total and surface expression of MchR1 on Ahi1 –/– neurons was similar to controls ( Ahi1 +/+). This indicates that a pathway for MchR1 trafficking to the surface plasma membrane is intact, but the process of targeting MchR1 into cilia is impaired in Ahi1-deficient mouse neurons, indicating a role for Ahi1 in localizing MchR1 to the cilium. Mouse Ahi1 –/– neurons that fail to accumulate MchR1 in the ciliary membrane have significant decreases in two downstream MchR1 signaling pathways [cAMP and extracellular signal-regulated kinase (Erk)] on MCH stimulation. These re...

Gravity is a pervasive environmental stimulus, and accurate graviception is required for optimal spatial orientation and postural stability. The primary graviceptors are the vestibular organs, which include angular velocity (semicircular canals) and linear acceleration (otolith organs) sensors. Graviception is degraded in patients with vestibular damage, resulting in spatial misperception and imbalance. Since minimal therapy is available for these patients, substantial effort has focused on developing a vestibular prosthesis or vestibular implant (VI) that reproduces information normally provided by the canals (since reproducing otolith function is very challenging technically). Prior studies demonstrated that angular eye velocity responses could be driven by canal VI-mediated angular head velocity information, but it remains unknown whether a canal VI could improve spatial perception and posture since these behaviors require accurate estimates of angular head position in space relative to gravity. Here, w...

The stromal interaction molecule 1 (STIM1) is an ER-Ca2+ sensor and an essential component of ER-Ca2+ store operated Ca2+ entry. Loss of STIM1 affects metabotropic glutamate receptor 1 (mGluR1)-mediated synaptic transmission, neuronal Ca2+ homeostasis, and intrinsic plasticity in Purkinje neurons (PNs). Long-term changes of intracellular Ca2+ signaling in PNs led to neurodegenerative conditions, as evident in individuals with mutations of the ER-Ca2+ channel, the inositol 1,4,5-triphosphate receptor. Here, we asked whether changes in such intrinsic neuronal properties, because of loss of STIM1, have an age-dependent impact on PNs. Consequently, we analyzed mRNA expression profiles and cerebellar morphology in PN-specific STIM1 KO mice ( STIM1PKO ) of both sexes across ages. Our study identified a requirement for STIM1-mediated Ca2+ signaling in maintaining the expression of genes belonging to key biological networks of synaptic function and neurite development among others. Gene expression changes correlat...

The integral capacity of human language together with semantic memory drives the linkage of words and their meaning, which theoretically is subject to cognitive control. However, it remains unknown whether, across different language modalities and input/output formats, there is a shared system in the human brain for word-meaning binding and how this system interacts with cognitive control. Here, we conducted a functional magnetic resonance imaging experiment based on a large cohort of subjects (50 females, 50 males) to comprehensively measure the brain responses evoked by semantic processing in spoken and written word comprehension and production tasks (listening, speaking, reading, and writing). We found that heteromodal word input and output tasks involved distributed brain regions within a frontal-parietal-temporal network and focally coactivated the anterior lateral visual word form area (VWFA), which is located in the basal occipitotemporal area. Directed connectivity analysis revealed that the VWFA w...