The Behavioral Tagging (BT) hypothesis provides crucial insights into the mechanism of long-term memory (LTM) consolidation. Novelty exposure in BT is a decisive step in activating the molecular machinery of memory formation. Several studies have validated BT utilizing different neurobehavioral tasks, however, the novelty given in all studies is open field (OF) exploration. Environment enrichment (EE) is another key experimental paradigm to explore the fundamentals of brain functioning. Recently, several studies have highlighted the importance of EE in enhancing cognition, LTM, and synaptic plasticity. Hence, in the present study, we investigated the effects of different types of novelty on LTM consolidation and PRP synthesis utilizing the BT phenomenon. Novel object recognition (NOR) was used as the learning task for rodents (male Wistar rats), while OF and EE were two types of novel experiences provided to the rodents. Our results indicated that EE exposure efficiently leads to LTM consolidation through ...

The nasal epithelium houses a population of solitary chemosensory cells (SCCs). SCCs express bitter taste receptors and taste transduction signaling components and are innervated by peptidergic trigeminal polymodal nociceptive nerve fibers. Thus, nasal SCCs respond to bitter compounds, including bacterial metabolites, and these reactions evoke protective respiratory reflexes and innate immune and inflammatory responses. We tested whether SCCs are implicated in aversive behavior to specific inhaled nebulized irritants using a custom-built dual-chamber forced-choice device. The behavior of mice was recorded and analyzed for the time spent in each chamber. Wild-type (WT) mice exhibited an aversion to 10 mM denatonium benzoate (Den) or cycloheximide and spent more time in the control (saline) chamber. The SCC-pathway knockout (KO) mice did not exhibit such an aversion response. The bitter avoidance behavior of WT mice was positively correlated with the concentration increase of Den and the number of exposures....

Previous investigation of cognitive processes using transcranial magnetic stimulation (TMS) have explored the response to different stimulation parameters such as frequency and coil location. In this study, we attempt to add another parameter by exploiting the spatial profiles of TMS coils to infer regional information concerning reward-related behavior. We used different TMS coils to modulate activity in the prefrontal cortex (PFC) and examined resulting changes in behavior and associated brain activity. More specifically, we used the Figure-8 coil to stimulate a portion of the dorsolateral PFC (DLPFC) and the H-Coil to stimulate a larger volume within the lateral PFC (LPFC). Healthy human volunteers completed behavioral questionnaires (n=29) or performed a reward-related decision-making fMRI task (n=21) immediately before and after acute high-frequency stimulation (10 Hz) with either a Figure-8 coil, H-Coil, or a sham coil. Stimulation was found to induce behavioral changes as well as changes in brain ...

The search for molecular underpinnings of human vocal communication has focused on genes encoding forkhead-box transcription factors, as rare disruptions of FOXP1, 2 and 4 have been linked to disorders involving speech and language deficits. In male songbirds, an animal model for vocal learning, experimentally altered expression levels of these transcription factors impair song production learning. The relative contributions of auditory processing, motor function or auditory-motor integration to the deficits observed after different FoxP manipulations in songbirds are unknown. To examine the potential effects on auditory learning and development, we focused on female zebra finches ( Taeniopygia guttata ) that do not sing but develop song memories, which can be assayed in operant preference tests. We tested whether the relatively high levels of FoxP1 expression in forebrain areas implicated in female song preference learning are crucial for the development and/or maintenance of this behaviour. Juvenile and ...

Despite exhibiting tau phosphorylation similar to Alzheimer disease, the human fetal brain is remarkably resilient to tau aggregation and toxicity. To identify potential mechanisms for this resilience, we used co-immunoprecipitation with mass spectrometry to characterize the tau interactome in human fetal, adult, and Alzheimer disease brains. We found significant differences between the tau interactome in fetal and AD brain tissue, with little difference between adult and AD, although these findings are limited by the low throughput and small sample size of these experiments. Differentially interacting proteins were enriched for 14-3-3 domains, and we found that the 14-3-3-β, η, and γ isoforms interacted with phosphorylated tau in Alzheimer disease but not the fetal brain. Since long isoform (4R) tau is only seen in the adult brain and this is one of the major differences between fetal and AD tau, we tested the ability of our strongest hit (14-3-3-β) to interact with 3R and 4R tau using co-immunoprecipitat...

Motor skill learning induces changes in synaptic structure and function in the primary motor cortex. In the Fragile X Syndrome (FXS) mouse model an impairment in motor skill learning and associated formation of new dendritic spines was previously reported. However, whether modulation of synaptic strength through trafficking of AMPA receptors with motor skill training is impaired in FXS is not known. Here we performed in vivo imaging of a tagged AMPA receptor subunit, GluA2, in layer (L) 2/3 neurons in the primary motor cortex of wild type and Fmr1 KO male mice at different stages of learning a single forelimb-reaching task. Surprisingly, in the Fmr1 KO mice, despite impairments in learning there was no deficit in motor skill training-induced spine formation. However, the gradual accumulation of GluA2 in WT stable spines, which persists after training is completed and past the phase of spine number normalization, is absent in the Fmr1 KO mouse. These results demonstrate that motor skill learning not only re...

How an odor is perceived is to a large extent dependent on the context in which that odor is (or has been) experienced. For example, experiencing an odor in mixture with taste during consumption can instill taste qualities in the percept of that odor (e.g., vanilla—an odor—has a gustatory quality: sweet). How associative features of odors are encoded in the brain remains unknown, but previous work suggests an important role for ongoing interactions between piriform cortex and extra-olfactory systems. Here we tested the hypothesis that piriform cortex dynamically encodes taste associations of odors. Rats were trained to associate one of two odors with saccharin; the other odor remained neutral. Before and after training, we tested preferences for the saccharin-associated odor versus the neutral odor, and recorded spiking responses from ensembles of neurons in posterior piriform cortex (pPC) to intra-oral delivery of small drops of the same odor solutions. The results show that animals successfully learned t...

Persistent neuronal firing is often observed in working memory and temporal association tasks both in humans and animals, and is believed to retain necessary information in these tasks. We have reported that hippocampal CA1 pyramidal cells are able to support persistent firing through intrinsic mechanisms in the presence of cholinergic agonists. However, it still remains largely unknown how persistent firing is affected by the development of animals and aging. Using in vitro patch-clamp recordings from CA1 pyramidal cells in rat brain slices, we first show that the cellular excitability of these aged rats was significantly lower than the young rats, responding with fewer spikes to current injection. In addition, we found age-dependent modulations of input resistance, membrane capacitance, and spike width. However, persistent firing in aged (~2 years old) rats was as strong as that in young animals, and the properties of persistent firing were very similar among different age groups. In addition, spike afte...

Wallerian Degeneration (WD) occurs in the early stages of numerous neurological disorders, and clarifying WD pathology is crucial for the advancement of neurological therapies. Adenosine triphosphate (ATP) is acknowledged as one of the key pathological substances in WD. The ATP-related pathological pathways that regulate WD have been defined. The elevation of ATP levels in axon contributes to delay WD and protects axons. While, ATP is necessary for the active processes to proceed WD, given that WD is stringently managed by auto-destruction programs. However, little is known about the bioenergetics during WD. In this study, we made sciatic nerve transection models for GO-ATeam2 knock-in rats and mice. We presented the spatiotemporal ATP distribution in the injured axons with in vivo ATP imaging systems, and investigated the metabolic source of ATP in the distal nerve stump. A gradual decrease in ATP levels was observed before the progression of WD. In addition, the glycolytic system and monocarboxylate tran...

Studies in cultured neurons have shown that neurofilaments are cargoes of axonal transport that move rapidly but intermittently along microtubule tracks. However, the extent to which axonal neurofilaments move in vivo has been controversial. Some researchers have proposed that most axonally transported neurofilaments are deposited into a persistently stationary network and that only a small proportion of axonal neurofilaments are transported in mature axons. Here we use the fluorescence photoactivation pulse-escape technique to test this hypothesis in intact peripheral nerves of adult male hThy1-paGFP-NFM mice, which express low levels of mouse neurofilament protein M tagged with photoactivatable GFP. Neurofilaments were photoactivated in short segments of large, myelinated axons and the mobility of these fluorescently tagged polymers was determined by analyzing the kinetics of their departure. Our results show that >80% of the fluorescence departed the window within 3 hours after activation, indicating a ...