How to build a cognitive map.

Learning and interpreting the structure of the environment is an innate feature of biological systems, and is integral to guiding flexible behaviors for evolutionary viability. The concept of a cognitive map has emerged as one of the leading metaphors for these capacities, and unraveling the learning and neural representation of such a map has become a central focus of neuroscience. In recent years, many models have been developed to explain cellular responses in the hippocampus and other brain areas. Because it can be difficult to see how these models differ, how they relate and what each model can contribute, this Review aims to organize these models into a clear ontology. This ontology reveals parallels between existing empirical results, and implies new approaches to understand hippocampal-cortical interactions and beyond.

Real-Time Single-Molecule Studies of RNA Polymerase-Promoter Open Complex Formation Reveal Substantial Heterogeneity Along the Promoter-Opening Pathway.

The expression of most bacterial genes commences with the binding of RNA polymerase (RNAP)-σ70 holoenzyme to the promoter DNA. This initial RNAP-promoter closed complex undergoes a series of conformational changes, including the formation of a transcription bubble on the promoter and the loading of template DNA strand into the RNAP active site; these changes lead to the catalytically active open complex (RPO) state. Recent cryo-electron microscopy studies have provided detailed structural insight on the RPO and putative intermediates on its formation pathway. Here, we employ single-molecule fluorescence microscopy to interrogate the conformational dynamics and reaction kinetics during real-time RPO formation on a consensus lac promoter. We find that the promoter opening may proceed rapidly from the closed to open conformation in a single apparent step, or may instead involve a significant intermediate between these states. The formed RPO complexes are also different with respect to their transcription bubble stability. The RNAP cleft loops, and especially the ß' rudder, stabilise the transcription bubble. The RNAP interactions with the promoter upstream sequence (beyond -35) stimulate transcription bubble nucleation and tune the reaction path towards stable forms of the RPO.

Reinforcement Learning: Full Glass or Empty - Depends Who You Ask.

An extension of the prediction error theory of dopamine, imported from artificial intelligence, represents the full distribution over future rewards rather than only the average and better explains dopamine responses.

Intuitive human interface to a scanning tunnelling microscope: observation of parity oscillations for a single atomic chain.

A new way to control individual molecules and monoatomic chains is devised by preparing a human-machine augmented system in which the operator and the machine are connected by a real-time simulation. Here, a 3D motion control system is integrated with an ultra-high vacuum (UHV) low-temperature scanning tunnelling microscope (STM). Moreover, we coupled a real-time molecular dynamics (MD) simulation to the motion control system that provides a continuous visual feedback to the operator during atomic manipulation. This allows the operator to become a part of the experiment and to make any adaptable tip trajectory that could be useful for atomic manipulation in three dimensions. The strength of this system is demonstrated by preparing and lifting a monoatomic chain of gold atoms from a Au(111) surface in a well-controlled manner. We have demonstrated the existence of Fabry-Pérot-type electronic oscillations in such a monoatomic chain of gold atoms and determined its phase, which was difficult to ascertain previously. We also show here a new geometric procedure to infer the adatom positions and therefore information about the substrate atoms, which are not easily visible on clean metallic surfaces such as gold. This method enables a new controlled atom manipulation technique, which we will refer to as point contact pushing (PCP) technique.

DIAGNOSTIC USE OF CRITTENDEN'S ATTACHMENT MEASURES IN FAMILY COURT IS NOT BEYOND A REASONABLE DOUBT.

We express serious doubt and cautioning regarding Spieker and Crittenden's (2010) claim that attachment measures associated with the dynamic-maturational model of attachment and adaptation (DMM; Crittenden, 2016) can be used for court decision-making. We demonstrate, using Crittenden's and coworkers' (e.g., Spieker & Crittenden, 2010) own data, that such measures have (a) insufficient reliability for use in individual diagnosis and (b) cannot retrodict maltreatment with sufficient sensitivity or specificity for court use. Just as atypical forms of attachment are sometimes observed among children reared adequately, typical (secure or mildly insecure) forms of attachment are sometimes observed among maltreated children and among children of caregivers struggling with psychopathology or socioeconomic adversity. The stakes are high, so it is imperative that court decisions accord with the rule of law. Certainty beyond a reasonable doubt is required, and DMM measures do not meet that requirement.

Pausing controls branching between productive and non-productive pathways during initial transcription in bacteria.

Transcription in bacteria is controlled by multiple molecular mechanisms that precisely regulate gene expression. It has been recently shown that initial RNA synthesis by the bacterial RNA polymerase (RNAP) is interrupted by pauses; however, the pausing determinants and the relationship of pausing with productive and abortive RNA synthesis remain poorly understood. Using single-molecule FRET and biochemical analysis, here we show that the pause encountered by RNAP after the synthesis of a 6-nt RNA (ITC6) renders the promoter escape strongly dependent on the NTP concentration. Mechanistically, the paused ITC6 acts as a checkpoint that directs RNAP to one of three competing pathways: productive transcription, abortive RNA release, or a new unscrunching/scrunching pathway. The cyclic unscrunching/scrunching of the promoter generates a long-lived, RNA-bound paused state; the abortive RNA release and DNA unscrunching are thus not as tightly linked as previously thought. Finally, our new model couples the pausing with the abortive and productive outcomes of initial transcription.

Dynamic modulation of activity in cerebellar nuclei neurons during pavlovian eyeblink conditioning in mice.

While research on the cerebellar cortex is crystallizing our understanding of its function in learning behavior, many questions surrounding its downstream targets remain. Here, we evaluate the dynamics of cerebellar interpositus nucleus (IpN) neurons over the course of Pavlovian eyeblink conditioning. A diverse range of learning-induced neuronal responses was observed, including increases and decreases in activity during the generation of conditioned blinks. Trial-by-trial correlational analysis and optogenetic manipulation demonstrate that facilitation in the IpN drives the eyelid movements. Adaptive facilitatory responses are often preceded by acquired transient inhibition of IpN activity that, based on latency and effect, appear to be driven by complex spikes in cerebellar cortical Purkinje cells. Likewise, during reflexive blinks to periocular stimulation, IpN cells show excitation-suppression patterns that suggest a contribution of climbing fibers and their collaterals. These findings highlight the integrative properties of subcortical neurons at the cerebellar output stage mediating conditioned behavior.