Parental care is critical for successful reproduction in mammals. Recent work has implicated the hormone prolactin in regulating male parental behavior, similar to its established role in females. Male laboratory mice show a mating-induced suppression of infanticide (normally observed in virgins) and onset of paternal behavior 2 weeks after mating. Using this model, we sought to investigate how prolactin acts in the forebrain to regulate paternal behavior. First, using c-fos immunoreactivity in prolactin receptor (Prlr) Prlr -IRES-Cre-tdtomato reporter mouse sires, we show that the circuitry activated during paternal interactions contains prolactin-responsive neurons in multiple sites, including the medial preoptic nucleus, bed nucleus of the stria terminalis, and medial amygdala. Next, we deleted Prlr from 3 prominent cell types found in these regions: glutamatergic, GABAergic, and CaMKIIα. Prlr-deletion from CaMKIIα, but not glutamatergic or GABAergic cells, had a profound effect on paternal behavior as ...

The human visual system consists of multiple topographic maps that extend from the early visual cortex (EVC) along the dorsal and ventral processing streams. Responses to illusory shapes within these maps have been demonstrated in the ventral stream areas, in particular the lateral occipital complex (LOC). Recently, the intraparietal sulcus (IPS) of the dorsal stream has been linked to the processing of illusory shapes defined by motion. It remains unclear whether the topographically organized parietal areas also respond to stationary illusory shapes, which would suggest their generic role in representing illusory content. In the current study we measured brain responses using fMRI while 30 human participants (12 male) observed flickering inducers around the fixation task. The inducers either formed an illusory diamond in the center, a triangle in the left or right hemifield, or were inverted such that no illusory figure was formed. We compared responses of parietal regions IPS0-IPS5 and SPL1 to each illus...

An increasing number of studies have shown that cross-modal interaction can occur in early sensory cortices. Yet, how neurons in sensory cortices integrate multisensory cues in perceptual tasks and to what extent this influences behavior is largely unclear. To investigate, we examined visual modulation of auditory responses in the primary auditory cortex (A1) in a two-alternative forced-choice task. During the task, male rats were required to make a behavioral choice based on the pure tone frequency (low vs. high) of the self-triggered stimulus to get a water reward. The result showed that the presence of a noninformative visual cue did not uniformly influence auditory response, with frequently enhancing just one of them. Closely correlated with behavioral choice, the visual cue mainly enhanced responsiveness to the auditory cue indicating a movement direction contralateral to A1 recorded. Operating in this fashion afforded A1 neurons a superior capability to discriminate sound during multisensory trials. ...

In vitro and in vivo experimentation in the central nervous system are effective approaches to study its functioning. Manipulations in vitro are characterized by easy experimental control and stable experimental conditions. However, transferring these advantages to in vivo research remains technically and ethically challenging, preventing many research teams from acquiring critical recordings in their animal models. In order to transfer the benefits of in vitro experimentation to in vivo experimentation, we developed a suite of 3d-printed tools (a superfusion chamber with an independent brain presser and animal stand). Using the immature rat barrel cortex as a model, we show that our set of tools (further ’superfusion preparation’) provides stable conditions for electrophysiological and neuroimaging recordings in the neonatal rat neocortex in vivo . Highly correlated intra- and extracellular activity was recorded during spontaneous and evoked cortical activity, supporting the possibility of simultaneous lo...

Thyroid hormones (THs), thyroxine (T4) and triiodothyronine (T3), regulate growth, metabolism, and neurodevelopment. THs secretion is controlled by the pituitary thyroid-stimulating hormone (TSH) and the hypothalamic-pituitary-thyroid (HPT) axis. The organic anion-transporting polypeptide 1C1 (OATP1C1/Slco1c1) and the monocarboxylate transporter 8 (MCT8/SLC16A2) actively transport THs, which bind to their nuclear receptors and induce gene expression. A mutation in OATP1C1 is associated with brain hypometabolism, gradual neurodegeneration, and impaired cognitive and motor functioning in adolescent patients. In order to understand the role of Oatp1c1 and the mechanisms of the disease, we profiled the transcriptome of oatp1c1 mutant ( oatp1c1-/- ) and mct8-/-xoatp1c1-/- adult male and female zebrafish brains. Among dozens of differentially expressed genes, agouti-related neuropeptide 1 ( agrp1 ) expression increased in oatp1c1-/- adult brains. Imaging in the hypothalamus revealed enhanced proliferation of Agr...

Considerable evidence from mouse models and human postmortem tissue suggests loss of Muscleblind-like protein 2 (MBNL2) function in brain is a major driver of central nervous system symptoms in Myotonic Dystrophy Type 1 (DM1). Increased hypersomnia, fatigue, and surgical complications associated with general anesthesia suggest possible sensitivity to GABAergic inhibition in DM1. To test the hypothesis that MBNL2 depletion leads to behavioral sensitivity to GABAA-R modulation, Mbnl2 KO and WT littermates were treated with the anesthetic sevoflurane, the benzodiazepine diazepam, the imidazopyridine zolpidem, and the benzodiazepine rescue agent, flumazenil (Ro 15-1788), and assessed for various behavioral metrics. Mbnl2 KO mice exhibited delayed recovery following sevoflurane, delayed emergence and recovery from zolpidem, and enhanced sleep time at baseline that was modulated by flumazenil (Ro 15-1788). A significantly higher proportion of Mbnl2 KO mice also loss their righting reflex (LORR) from a standard d...

Low-frequency (<200 Hz), subperception spinal cord stimulation (SCS) is a novel modality demonstrating therapeutic efficacy for treating chronic neuropathic pain. When stimulation parameters were carefully titrated, patients experienced rapid onset (seconds – minutes) pain relief without paresthesia, but the mechanisms of action are unknown. Using an integrated computational model and in vivo measurements in urethane-anesthetized rats, we quantified how stimulation parameters (placement, pulse width, frequency, and amplitude) influenced dorsal column (DC) axon activation and neural responses in the dorsal horn (DH). Both modeled and recorded DC axons responded with irregular spiking patterns in response to low-amplitude SCS. Maximum inhibition of DH neurons occurred at ∼80% of the predicted sensory threshold in both modeled and recorded neurons, and responses were strongly dependent on spatially targeting of stimulation, i.e., the complement of DC axons activated, and on stimulation parameters. Intrathecal...

Costanza Angelini, Alessandro Morellato, Annalisa Alfieri, Lisa Pavinato, Tiziana Cravero, et al. (see pages [7183–7200][1]) The postsynaptic density (PSD) of excitatory synapses contains an extraordinary number of proteins, including AMPA and NMDA receptors, accessory proteins that regulate

Task representations are critical for cognitive control and adaptive behavior. The hierarchical organization of task representations allows humans to maintain goals, integrate information across varying contexts, and select potential responses. In this study we characterized the structure and interactive dynamics of task representations that facilitate cognitive control. Human participants (both males and females) performed a hierarchical task that required them to select a response rule while considering the contingencies from different contextual inputs. By applying time- and frequency-resolved representational similarity analysis to human electroencephalography data, we characterized properties of task representations that are otherwise difficult to observe. We found that participants formed multiple representations of task-relevant contexts and features from the presented stimuli, beyond simple stimulus–response mappings. These disparate representations were hierarchically structured, with higher-order...

The mitochondrial anchor syntaphilin (SNPH) is a key mitochondrial protein normally expressed in axons to maintain neuronal health by positioning mitochondria along axons for metabolic needs. However, in 2019 we discovered a novel form of excitotoxicity that results when SNPH is misplaced into neuronal dendrites in disease models. A key unanswered question about this SNPH excitotoxicity is the pathologic molecules that trigger misplacement or intrusion of SNPH into dendrites. Here, we identified two different classes of pathologic molecules that interact to trigger dendritic SNPH intrusion. Using primary hippocampal neuronal cultures from mice of either sex, we demonstrated that the pro-inflammatory cytokine IL-1β interacts with NMDA to trigger SNPH intrusion into dendrites. First, IL-1β and NMDA each individually triggers dendritic SNPH intrusion. Second, IL-1β and NMDA do not act independently but interact. Thus, blocking NMDAR by the antagonist MK-801 blocks IL-1β from triggering dendritic SNPH intrusio...