Among the modulatory functions of thyrotropin-releasing hormone (TRH), an anorectic behavior in rodents is observed when centrally injected. Hypothalamic PVN neurons receive serotonergic inputs from dorsal raphe nucleus and express serotonin (5HT) receptors such as 5HT1A, 5HT2A/2C, 5HT6, which are involved in 5HT-induced feeding regulation. Rats subjected to dehydration-induced anorexia (DIA) model show increased PVN TRH mRNA expression, associated with their decreased food intake. We analyzed whether 5HT input is implicated in the enhanced PVN TRH transcription that anorectic rats exhibit, given that 5HT increases TRH expression and release when studied in vitro . By using mHypoA-2/30 hypothalamic cell cultures, we found that 5HT stimulated TRH mRNA, pCREB and pERK1/2 levels. By inhibiting basal PKA or PKC activities or those induced by 5HT, pCREB or pERK1/2 content did not increase suggesting involvement of both kinases in their phosphorylation. 5HT effect on TRH mRNA was not affected by PKA inhibition, ...

Visual word recognition has been proposed to have a functional and spatial organization corresponding to hierarchical language-like word forms in the left fusiform gyrus (FG) during visual word recognition in alphabetic languages. However, it is still unclear whether the similar functional gradients of word-like representation exist during Chinese character recognition. In this study, we adopted univariate activation analysis and representational similarity analysis (RSA) methods to investigate the functional organization in the FG for Chinese character recognition using task fMRI data. Native Chinese readers were visually presented with four types of character-like stimuli (i.e., real characters, pseudo-characters, false characters, and stroke combinations). After analysis, we observed a posterior-to-anterior functional gradient in the left FG corresponding to the degree of likeness of stimuli to character. Additionally, distinct sub-regions of the left FG harbor different orthographic codes. The middle p...

Recent theories of autism propose that a core deficit in autism would be a less context-sensitive weighting of prediction errors. There is also first support for this hypothesis on an early sensory level. However, an open question is whether this decreased context sensitivity is caused by faster updating of one's model of the world (i.e., higher weighting of new information), proposed by predictive coding theories, or slower model updating. Here, we differentiated between these two hypotheses by investigating how first impressions shape the mismatch negativity (MMN), reflecting early sensory prediction error processing. An autism and matched control group of human adults (both n = 27, 8 female) were compared on the multi-timescale MMN paradigm, in which tones were presented that were either standard (frequently occurring) or deviant (rare), and these roles reversed every block. A well-replicated observation is that the initial model (i.e., the standard and deviant sound in the first block) influences MMN a...

Danielle Stanton-Turcotte, Karolynn Hsu, Samantha A. Moore, Makiko Yamada, James P. Fawcett, et al. (see pages [3931–3948][1]) MLLT11 is a 90 aa protein that was first identified because its gene was translocated and fused to the mixed-lineage leukemia (MLL) gene in two children with pediatric

Oxytocin receptors (OTR) have been found in the paraventricular thalamus (PVT) for the regulation of feeding and maternal behaviors. However, the functional projections of OTR-expressing PVT neurons remain largely unknown. Here, we used chemogenetic and optogenetic tools to test the role of OTR-expressing PVT neurons and their projections in the regulation of food intake in both male and female OTR-Cre mice. We found chemogenetic activation of OTR-expressing PVT neurons promoted food seeking under trials with a progressive ratio schedule of reinforcement. Using Feeding Experimentation Devices for real-time meal measurements, we found chemogenetic activation of OTR-expressing PVT neurons increased meal frequency but not cumulative food intake because of a compensatory decrease in meal sizes. In combination with anterograde neural tracing and slice patch-clamp recordings, we found optogenetic stimulation of PVT OTR terminals excited neurons in the posterior basolateral amygdala (pBLA) and nucleus accumbens c...

Steady-state visually evoked potentials (SSVEPs) are widely used to index top-down cognitive processing in human electroencephalogram (EEG) studies. Typically, two stimuli flickering at different temporal frequencies (TFs) are presented, each producing a distinct response in the EEG at its flicker frequency. However, how SSVEP responses in EEGs are modulated in the presence of a competing flickering stimulus just because of sensory interactions is not well understood. We have previously shown in local field potentials (LFPs) recorded from awake monkeys that when two overlapping full-screen gratings are counterphased at different TFs, there is an asymmetric SSVEP response suppression, with greater suppression from lower TFs, which further depends on the relative orientations of the gratings (stronger suppression and asymmetry for parallel compared with orthogonal gratings). Here, we first confirmed these effects in both male and female human EEG recordings. Then, we mapped the response suppression of one st...

The formation of connections within the mammalian neocortex is highly regulated by both extracellular guidance mechanisms and intrinsic gene expression programs. There are two types of cortical projection neurons (CPNs): those that project locally and interhemispherically and those that project to subcerebral structures such as the thalamus, hindbrain, and spinal cord. The regulation of cortical projection morphologies is not yet fully understood at the molecular level. Here, we report a role for Mllt11 (Myeloid/lymphoid or mixed-lineage leukemia; translocated to chromosome 11/All1 Fused Gene From Chromosome 1q) in the migration and neurite outgrowth of callosal projection neurons during mouse brain formation. We show that Mllt11 expression is exclusive to developing neurons and is enriched in the developing cortical plate (CP) during the formation of the superficial cortical layers. In cultured primary cortical neurons, Mllt11 is detected in varicosities and growth cones as well as the soma. Using conditi...

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson’s disease (PD), but the pathogenic mechanism underlying LRRK2 mutations remains unresolved. In this study, we investigate the consequence of inactivation of LRRK2 and its functional homolog LRRK1 in male and female mice up to 25 months of age using behavioral, neurochemical, neuropathological, and ultrastructural analyses. We report that LRRK1 and LRRK2 double knock-out ( LRRK DKO) mice exhibit impaired motor coordination at 12 months of age before the onset of DA neuron loss in the substantia nigra (SNpc). Moreover, LRRK DKO mice develop age-dependent, progressive loss of DA terminals in the striatum. Evoked dopamine release measured by fast-scan cyclic voltammetry in the dorsal striatum is also reduced in the absence of LRRK. Furthermore, LRRK DKO mice at 20–25 months of age show substantial loss of DA neurons in the SNpc. The surviving SNpc neurons in LRRK DKO mice at 25 months of age accumulate large number...

The functions of cortical networks are progressively established during development by series of events shaping the neuronal connectivity. Synaptic elimination, which consists of removing the supernumerary connections generated during the earlier stages of cortical development, is one of the latest stages in neuronal network maturation. The Semaphorin 3F co-receptors Neuropilin 2 (Nrp2) and Plexin-A3 (PlxnA3) may play an important role in the functional maturation of the cerebral cortex by regulating the excess dendritic spines on cortical excitatory neurons. Yet, the identity of the connections eliminated under the control of Nrp2/PlxnA3 signaling is debated and the importance of this synaptic refinement for cortical functions remains poorly understood. Here, we show that Nrp2/PlxnA3 controls the spine densities in layer 4 (L4) and on the apical dendrite of layer 5 (L5) neurons of the sensory and motor cortices. Using a combination of neuroanatomical, ex vivo electrophysiology and in vivo functional imagi...