Neural mechanisms underlying uninstructed orofacial movements during reward-based learning behaviors.

During reward-based learning tasks, animals make orofacial movements that globally influence brain activity at the timings of reward expectation and acquisition. These orofacial movements are not explicitly instructed and typically appear along with goal-directed behaviors. Here, we show that reinforcing optogenetic stimulation of dopamine neurons in the ventral tegmental area (oDAS) in mice is sufficient to induce orofacial movements in the whiskers and nose without accompanying goal-directed behaviors.

Allocentric representations of space in the hippocampus.

The hippocampal-entorhinal system is essential for navigation and memory. The first description of spatially tuned place cell activity in area CA1 of the hippocampus suggested that spatial representations are not centered on self, but are rather allocentric. This idea is supported by extensive neurophysiological data, including temporally coordinated sequential activity during theta phase precession and sharp wave ripples.

Spatial representations of self and other in the hippocampus.

An animal's awareness of its location in space depends on the activity of place cells in the hippocampus. How the brain encodes the spatial position of others has not yet been identified. We investigated neuronal representations of other animals' locations in the dorsal CA1 region of the hippocampus with an observational T-maze task in which one rat was required to observe another rat's trajectory to successfully retrieve a reward.

Nuclear-translocated Glyceraldehyde-3-phosphate Dehydrogenase Promotes Poly(ADP-ribose) Polymerase-1 Activation during Oxidative/Nitrosative Stress in Stroke.

In addition to its role in DNA repair, nuclear poly(ADP-ribose) polymerase-1 (PARP-1) mediates brain damage when it is over-activated by oxidative/nitrosative stress. Nonetheless, it remains unclear how PARP-1 is activated in neuropathological contexts. Here we report that PARP-1 interacts with a pool of glyceradehyde-3-phosphate dehydrogenase (GAPDH) that translocates into the nucleus under oxidative/nitrosative stress both in vitro and in vivo.

Aversive behavior induced by optogenetic inactivation of ventral tegmental area dopamine neurons is mediated by dopamine D2 receptors in the nucleus accumbens.

Dopamine (DA) transmission from the ventral tegmental area (VTA) is critical for controlling both rewarding and aversive behaviors. The transient silencing of DA neurons is one of the responses to aversive stimuli, but its consequences and neural mechanisms regarding aversive responses and learning have largely remained elusive. Here, we report that optogenetic inactivation of VTA DA neurons promptly down-regulated DA levels and induced up-regulation of the neural activity in the nucleus accumbens (NAc) as evaluated by Fos expression.

Use of "MGE enhancers" for labeling and selection of embryonic stem cell-derived medial ganglionic eminence (MGE) progenitors and neurons.

The medial ganglionic eminence (MGE) is an embryonic forebrain structure that generates the majority of cortical interneurons. MGE transplantation into specific regions of the postnatal central nervous system modifies circuit function and improves deficits in mouse models of epilepsy, Parkinson's disease, pain, and phencyclidine-induced cognitive deficits. Herein, we describe approaches to generate MGE-like progenitor cells from mouse embryonic stem (ES) cells.

Distinct roles of segregated transmission of the septo-habenular pathway in anxiety and fear.

The posterior septum consisting of the triangular septum (TS) and the bed nucleus of the anterior commissure (BAC) is predominantly linked with the medial habenula (MHb) and has been implicated in the control of anxiety and fear responses. However, its anatomical and functional linkage has largely remained elusive. We established a transgenic mouse model in which the TS and BAC projection neurons were visualized by GFP fluorescence and selectively eliminated by immunotoxin-mediated cell targeting.

Robust formation and maintenance of continuous stratified cortical neuroepithelium by laminin-containing matrix in mouse ES cell culture.

In the mammalian cortex, the dorsal telencephalon exhibits a characteristic stratified structure. We previously reported that three-dimensional (3D) culture of mouse ES cells (mESCs) can efficiently generate cortical neuroepithelium (NE) and layer-specific cortical neurons. However, the cortical NE generated in this mESC culture was structurally unstable and broke into small neural rosettes by culture day 7, suggesting that some factors for reinforcing the structural integrity were missing.

Pathway-specific modulation of nucleus accumbens in reward and aversive behavior via selective transmitter receptors.

The basal ganglia-thalamocortical circuitry plays a central role in selecting actions that achieve reward-seeking outcomes and avoid aversive ones. Inputs of the nucleus accumbens (NAc) in this circuitry are transmitted through two parallel pathways: the striatonigral direct pathway and the striatopallidal indirect pathway. In the NAc, dopaminergic (DA) modulation of the direct and the indirect pathways is critical in reward-based and aversive learning and cocaine addiction.

Pathway-specific control of reward learning and its flexibility via selective dopamine receptors in the nucleus accumbens.

In the basal ganglia, inputs from the nucleus accumbens (NAc) are transmitted through both direct and indirect pathways and control reward-based learning. In the NAc, dopamine (DA) serves as a key neurotransmitter, modulating these two parallel pathways. This study explored how reward learning and its flexibility are controlled in a pathway-specific and DA receptor-dependent manner.

Subregional specification of embryonic stem cell-derived ventral telencephalic tissues by timed and combinatory treatment with extrinsic signals.

During early telencephalic development, the major portion of the ventral telencephalic (subpallial) region becomes subdivided into three regions, the lateral (LGE), medial (MGE), and caudal (CGE) ganglionic eminences. In this study, we systematically recapitulated subpallial patterning in mouse embryonic stem cell (ESC) cultures and investigated temporal and combinatory actions of patterning signals. In serum-free floating culture, the dorsal-ventral specification of ESC-derived telencephalic neuroectoderm is dose-dependently directed by Sonic hedgehog (Shh) signaling.