Response to correspondence to Hale et al. atypical phenotypes associated with pathogenic CHD7 variants and a proposal for broadening CHARGE syndrome clinical diagnostic criteria

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134796/1/ajmga37629_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134796/2/ajmga37629.pd

Epigenetics and Language: The Minimalist Program, Connectionism and Biology

Chomsky claims that linguistics should be thought of as a branch of biology. Lorenzo and Longa claim that the Minimalist Program is better than previous approaches at connecting language to biology because it relies on epigenetic processes in development, which is the current trend in biology. Epigenetic processes alter gene expression in a heritable manner without changing DNA sequence. Recently, biologists have come to see epigenetics as extremely important to development. We agree with Lorenzo and Longa that inclusion of epigenetic processes in linguists' theories of language development is important if linguists desire unification with biology. However, Lorenzo and Longa do not discuss processes that alter gene expression in a heritable manner without altering DNA. A close examination of their position illuminates a large gap between the Minimalist Program and epigenetics. In contrast, there is a relatively small gap between connectionism and epigenetics. Language development in connectionist systems involves modifications of neural connections. Research shows that modification of neural connections involves processes that alter gene expression without altering DNA. It follows that connectionism is the superior paradigm for researchers interested in unification between biology and linguistics

In Vivo Spike-Timing-Dependent Plasticity in the Optic Tectum of Xenopus Laevis

Spike-timing-dependent plasticity (STDP) is found in vivo in a variety of systems and species, but the first demonstrations of in vivo STDP were carried out in the optic tectum of Xenopus laevis embryos. Since then, the optic tectum has served as an excellent experimental model for studying STDP in sensory systems, allowing researchers to probe the developmental consequences of this form of synaptic plasticity during early development. In this review, we will describe what is known about the role of STDP in shaping feed-forward and recurrent circuits in the optic tectum with a focus on the functional implications for vision. We will discuss both the similarities and differences between the optic tectum and mammalian sensory systems that are relevant to STDP. Finally, we will highlight the unique properties of the embryonic tectum that make it an important system for researchers who are interested in how STDP contributes to activity-dependent development of sensory computations

Optogenetic activation of parvalbumin and somatostatin interneurons selectively restores theta-nested gamma oscillations and oscillation-induced spike timing-dependent long-term potentiation impaired by amyloid β oligomers

BACKGROUND: Abnormal accumulation of amyloid β1-42 oligomers (AβO1-42), a hallmark of Alzheimer's disease, impairs hippocampal theta-nested gamma oscillations and long-term potentiation (LTP) that are believed to underlie learning and memory. Parvalbumin-positive (PV) and somatostatin-positive (SST) interneurons are critically involved in theta-nested gamma oscillogenesis and LTP induction. However, how AβO1-42 affects PV and SST interneuron circuits is unclear. Through optogenetic manipulation of PV and SST interneurons and computational modeling of the hippocampal neural circuits, we dissected the contributions of PV and SST interneuron circuit dysfunctions on AβO1-42-induced impairments of hippocampal theta-nested gamma oscillations and oscillation-induced LTP. RESULTS: Targeted whole-cell patch-clamp recordings and optogenetic manipulations of PV and SST interneurons during in vivo-like, optogenetically induced theta-nested gamma oscillations in vitro revealed that AβO1-42 causes synapse-specific dysfunction in PV and SST interneurons. AβO1-42 selectively disrupted CA1 pyramidal cells (PC)-to-PV interneuron and PV-to-PC synapses to impair theta-nested gamma oscillogenesis. In contrast, while having no effect on PC-to-SST or SST-to-PC synapses, AβO1-42 selectively disrupted SST interneuron-mediated disinhibition to CA1 PC to impair theta-nested gamma oscillation-induced spike timing-dependent LTP (tLTP). Such AβO1-42-induced impairments of gamma oscillogenesis and oscillation-induced tLTP were fully restored by optogenetic activation of PV and SST interneurons, respectively, further supporting synapse-specific dysfunctions in PV and SST interneurons. Finally, computational modeling of hippocampal neural circuits including CA1 PC, PV, and SST interneurons confirmed the experimental observations and further revealed distinct functional roles of PV and SST interneurons in theta-nested gamma oscillations and tLTP induction. CONCLUSIONS: Our results reveal that AβO1-42 causes synapse-specific dysfunctions in PV and SST interneurons and that optogenetic modulations of these interneurons present potential therapeutic targets for restoring hippocampal network oscillations and synaptic plasticity impairments in Alzheimer's disease

Measuring large-scale structure with quasars in narrow-band filter surveys

We show that a large-area imaging survey using narrow-band filters could detect quasars in sufficiently high number densities, and with more than sufficient accuracy in their photometric redshifts, to turn them into suitable tracers of large-scale structure. If a narrow-band optical survey can detect objects as faint as i=23, it could reach volumetric number densities as high as 10^{-4} h^3 Mpc^{-3} (comoving) at z~1.5 . Such a catalog would lead to precision measurements of the power spectrum up to z~3-4. We also show that it is possible to employ quasars to measure baryon acoustic oscillations at high redshifts, where the uncertainties from redshift distortions and nonlinearities are much smaller than at z<1. As a concrete example we study the future impact of J-PAS, which is a narrow-band imaging survey in the optical over 1/5 of the unobscured sky with 42 filters of ~100 A full-width at half-maximum. We show that J-PAS will be able to take advantage of the broad emission lines of quasars to deliver excellent photometric redshifts, \sigma_{z}~0.002(1+z), for millions of objects.Comment: Matches version published in MNRAS (2012

ConSpec: honing in on critical steps for rapid learning and generalization in RL

In real life, success is often contingent upon multiple critical steps that are distant in time from each other and from the final reward. These critical steps are challenging to identify with traditional reinforcement learning (RL) methods that rely on the Bellman equation for credit assignment. Here, we present a new RL algorithm that uses offline contrastive learning to hone in on critical steps. This algorithm, which we call contrastive introspection (ConSpec), can be added to any existing RL algorithm. ConSpec learns a set of prototypes for the critical steps in a task by a novel contrastive loss and delivers an intrinsic reward when the current state matches one of these prototypes. The prototypes in ConSpec provide two key benefits for credit assignment: (1) They enable rapid identification of all the critical steps. (2) They do so in a readily interpretable manner, enabling out-of-distribution generalization when sensory features are altered. Distinct from other contemporary RL approaches to credit assignment, ConSpec takes advantage of the fact that it is easier to retrospectively identify the small set of steps that success is contingent upon than it is to prospectively predict reward at every step taken in the environment. Altogether, ConSpec improves learning in a diverse set of RL tasks, including both those with explicit, discrete critical steps and those with complex, continuous critical steps