Visual attention to features and space in mice using reverse correlation.

Visual attention allows the brain to evoke behaviors based on the most important visual features. Mouse models offer immense potential to gain a circuit-level understanding of this phenomenon, yet how mice distribute attention across features and locations is not well understood. Here, we describe a new approach to address this limitation by training mice to detect weak vertical bars in a background of dynamic noise while spatial cues manipulate their attention. By adapting a reverse-correlation method from human studies, we linked behavioral decisions to stimulus features and locations. We show that mice deployed attention to a small rostral region of the visual field. Within this region, mice attended to multiple features (orientation, spatial frequency, contrast) that indicated the presence of weak vertical bars. This attentional tuning grew with training, multiplicatively scaled behavioral sensitivity, approached that of an ideal observer, and resembled the effects of attention in humans. Taken together, we demonstrate that mice can simultaneously attend to multiple features and locations of a visual stimulus.

Gonadotrophin-releasing hormone and kisspeptin: It takes two to tango.

Kisspeptin (Kp), a family of peptides comprising products of the Kiss1 gene, was discovered 20 years ago; it is recognised as the major factor controlling the activity of the gonadotrophin-releasing hormone (GnRH) neurones and thus the activation of the reproductive axis in mammals. It has been widely documented that the effects of Kp on reproduction through its action on GnRH neurones are mediated by the GPR54 receptor. Kp controls the activation of the reproductive axis at puberty, maintains reproductive axis activity in adults and is involved in triggering ovulation in some species. Although there is ample evidence coming from both conditional knockout models and conditional-induced Kp neurone death implicating the Kp/GPR54 pathway in the control of reproduction, the mechanism(s) underlying this process may be more complex than a sole direct control of GnRH neuronal activity by Kp. In this review, we provide an overview of the recent advances made in elucidating the interplay between Kp- and GnRH- neuronal networks with respect to regulating the reproductive axis. We highlight the existence of a possible mutual regulation between GnRH and Kp neurones, as well as the implication of Kp-dependent volume transmission in this process. We also discuss the capacity of heterodimerisation between GPR54 and GnRH receptor (GnRH-R) and its consequences on signalling. Finally, we illustrate the role of mathematical modelling that accounts for the synergy between GnRH-R and GPR54 in explaining the role of these two receptors when defining GnRH neuronal activity and GnRH pulsatile release.

How Pulsatile Kisspeptin Stimulation and GnRH Autocrine Feedback Can Drive GnRH Secretion: A Modeling Investigation.

Pulsatile secretion of GnRH from hypothalamic GnRH neurons tightly regulates the release of mammalian reproductive hormones. Although key factors such as electrical activity and stimulation by kisspeptin have been extensively studied, the underlying mechanisms that regulate GnRH release are still not fully understood. Previously developed mathematical models studied hormonal release and electrical properties of GnRH neurons separately, but they never integrated both components. Herein, we present a more complete biophysical model to investigate how electrical activity and hormonal release interact. The model consists of two components: an electrical submodel comprised of a modified Izhikevich formalism incorporating several key ionic currents to reproduce GnRH neuronal bursting behavior, and a hormonal submodel that incorporates pulsatile kisspeptin stimulation and a GnRH autocrine feedback mechanism. Using the model, we examine the electrical activity of GnRH neurons and how kisspeptin affects GnRH pulsatility. The model reproduces the noise-driven bursting behavior of GnRH neurons as well as the experimentally observed electrophysiological effects induced by GnRH and kisspeptin. Specifically, the model reveals that external application of GnRH causes a transient hyperpolarization followed by an increase in firing frequency, whereas administration of kisspeptin leads to long-lasting depolarization of the neuron. The model also shows that GnRH release follows a pulsatile profile similar to that observed experimentally and that kisspeptin and GnRH exhibit ∼7-1 locking in their pulsatility. These results suggest that external kisspeptin stimulation with a period of ∼8 minutes drives the autocrine mechanism beyond a threshold to generate pronounced GnRH pulses every hour.