Two key features endow Drosophila Down syndrome cell adhesion molecule 1 (Dscam1) with the potential to provide a ubiquitous code for neuronal arbor self-avoidance. First, Dscam1 contains three large cassettes of alternative exons, so that stochastic alternative splicing yields 19,008 Dscam1 isoforms with different Ig ectodomains. Second, each neuron expresses a different subset of Dscam1 isoforms, and isoform-specific homophilic binding causes repulsion. This results in even spacing of self-arbors, while processes of other neurons can intermingle and share the same synaptic partners. In principle, this Dscam1 code could ensure arbor spacing of all neurons in Drosophila . This model is strongly supported by studies on dendrite spacing in the peripheral nervous system and studies on axonal branch segregation during brain development. However, the situation is less clear for central neuron dendrites, the major substrate for synaptic input in the CNS. We systematically tested the role of Dscam1 for dendrite g...

The entopeduncular nucleus (EPN) and substantia nigra pars reticulata (SNr) constitute the output nuclei of the basal ganglia, but studies on the EPN are limited compared with those on the SNr. Both nuclei receive projections from the striatum with axons containing substance P (SP) and cannabinoid type-1 receptor (CB1R), and immunoreactivities for these substances show complementary patterns in the striatum and SNr. In this study, we revealed a similar complementarity in the mouse EPN, combined it with region-specific neuronal distributions, and defined subregions of the EPN. First, the EPN was divided into two areas, one showing low SP and high CB1R (lSP/hCB1R) immunoreactivities, and the other showing high SP and low CB1R (hSP/lCB1R). The former received inputs from the dorsolateral striatum that are innervated by sensorimotor cortices, whereas the latter received inputs from the medial striatum that are innervated by limbic/association cortices. Then, the lSP/hCB1R area was further divided into the dors...

Forgetting is important for animals to manage acquired memories to enable adaptation to changing environments; however, the neural network in mechanisms of forgetting is not fully understood. To understand the mechanisms underlying forgetting, we examined olfactory adaptation, a form of associative learning, in Caenorhabditis elegans . The forgetting of diacetyl olfactory adaptation in C. elegans is regulated by secreted signals from AWC sensory neurons via the TIR-1/JNK-1 pathway. These signals cause a decline of the sensory memory trace in AWA neurons, where diacetyl is mainly sensed. To further understand the neural network that regulates this forgetting, we investigated the function of interneurons downstream of AWA and AWC neurons. We found that a pair of interneurons, AIA, is indispensable for the proper regulation of behavioral forgetting of diacetyl olfactory adaptation. Loss or inactivation of AIA caused the impairment of the chemotaxis recovery after adaptation without causing severe chemotaxis d...

In the article, “Histochemical Characterization of the Dorsal Raphe-Periaqueductal Grey Dopamine Transporter Neurons Projecting to the Extended Amygdala,” by Qin Zhao, Tetsufumi Ito, Chika Soko, Yoshie Hori, Takafumi Furuyama, Hiroyuki Hioki, Kohtarou …

Episodic memory is a recollection of past personal experiences associated with particular times and places. This kind of memory is commonly subject to loss of contextual information or “semantization,” which gradually decouples the encoded memory items from their associated contexts while transforming them into semantic or gist-like representations. Novel extensions to the classical Remember/Know (R/K) behavioral paradigm attribute the loss of episodicity to multiple exposures of an item in different contexts. Despite recent advancements explaining semantization at a behavioral level, the underlying neural mechanisms remain poorly understood. In this study, we suggest and evaluate a novel hypothesis proposing that Bayesian–Hebbian synaptic plasticity mechanisms might cause semantization of episodic memory. We implement a cortical spiking neural network model with a Bayesian–Hebbian learning rule called Bayesian Confidence Propagation Neural Network (BCPNN), which captures the semantization phenomenon and o...

Estrogen plays fundamental roles in nervous system development and function. Traditional studies examining the effect of estrogen in the brain have focused on the nuclear estrogen receptors (ERs), ERα and ERβ. Studies related to the extranuclear, membrane-bound G-protein-coupled ER (GPER/GPR30) have revealed a neuroprotective role for GPER in mature neurons. In this study, we investigated the differential effects of GPER activation in primary rat embryonic day 18 (E18) hippocampal and cortical neurons. Microscopy imaging, multielectrode array (MEA), and Ca2+ imaging experiments revealed that GPER activation with selective agonist, G-1, and nonselective agonist, 17β-estradiol (E2), increased neural growth, neural firing activity, and intracellular Ca2+ more profoundly in hippocampal neurons than in cortical neurons. The GPER-mediated Ca2+ rise in hippocampal neurons involves internal Ca2+ store release via activation of phospholipase C (PLC) and extracellular entry via Ca2+ channels. Immunocytochemistry res...

Model selection is often implicit: when performing an ANOVA, one assumes that the normal distribution is a good model of the data; fitting a tuning curve implies that an additive and a multiplicative scaler describes the behavior of the neuron; even calculating an average implicitly assumes that the data were sampled from a distribution that has a finite first statistical moment: the mean. Model selection may be explicit, when the aim is to test whether one model provides a better description of the data than a competing one. As a special case, clustering algorithms identify groups with similar properties within the data. They are widely used from spike sorting to cell type identification to gene expression analysis. We discuss model selection and clustering techniques from a statistician’s point of view, revealing the assumptions behind, and the logic that governs the various approaches. We also showcase important neuroscience applications and provide suggestions how neuroscientists could put model select...

In human and nonhuman primates, reflexive tracking eye movements can be initiated at very short latency in response to a rapid shift of the image. Previous studies in humans have shown that only a part of the central visual field is optimal for driving ocular following responses. Herein, we have investigated spatial summation of motion information, across a wide range of spatial frequencies and speeds of drifting gratings by recording short-latency ocular following responses in macaque monkeys. We show that the optimal stimulus size for driving ocular responses cover a small (diameter, <20°), central part of the visual field that shrinks with higher spatial frequency. This signature of linear motion integration remains invariant with speed and temporal frequency. For low and medium spatial frequencies, we found a strong suppressive influence from surround motion, evidenced by a decrease of response amplitude for stimulus sizes larger than optimal. Such suppression disappears with gratings at high frequenci...

It is well known that hippocampal place cells have spatiotemporal properties, namely, that they generally respond to a single spatial location of a small environment, and they also display the temporal response property of theta phase precession, namely, that the phase of spiking relative to the theta wave shifts from the late phase to early phase as the animal crosses the place field. Grid cells in Layer II of the medial entorhinal cortex (MEC) also have spatiotemporal properties similar to hippocampal place cells, except that grid cells respond to multiple spatial locations that form a hexagonal pattern. Because the EC is the upstream area that projects strongly to the hippocampus, a number of EC-hippocampus learning models have been proposed to explain how the spatial receptive field properties of place cells emerge via synaptic plasticity. However, the question of how the phase precession properties of place cells and grid cells are related has remained unclear. This study shows how theta phase precess...

Arginine vasopressin (AVP) serves as a neuromodulator in the brain. The hippocampus is one of the major targets for AVP, as it has been demonstrated that the hippocampus receives vasopressinergic innervation and expresses AVP receptors. The dentate gyrus (DG) granule cells (GCs) serve as a gate governing the inflow of information to the hippocampus. High densities of AVP receptors are expressed in the DG GCs. However, the roles and the underlying cellular and molecular mechanisms of AVP in the DG GCs have not been determined. We addressed this question by recording from the DG GCs in rat hippocampal slices. Our results showed that application of AVP concentration-dependently evoked an inward holding current recorded from the DG GCs. AVP depolarized the DG GCs and increased their action potential firing frequency. The excitatory effects of AVP were mediated by activation of V1a receptors and required the function of phospholipase Cβ (PLCβ). Whereas intracellular Ca2+ release and protein kinase C activity we...