Discrimination learning with variable stimulus 'salience'.

BACKGROUND: In nature, sensory stimuli are organized in heterogeneous combinations. Salient items from these combinations 'stand-out' from their surroundings and determine what and how we learn. Yet, the relationship between varying stimulus salience and discrimination learning remains unclear. PRESENTATION OF THE HYPOTHESIS: A rigorous formulation of the problem of discrimination learning should account for varying salience effects. We hypothesize that structural variations in the environment where the conditioned stimulus (CS) is embedded will be a significant determinant of learning rate and retention level. TESTING THE HYPOTHESIS: Using numerical simulations, we show how a modified version of the Rescorla-Wagner model, an influential theory of associative learning, predicts relevant interactions between varying salience and discrimination learning. IMPLICATIONS OF THE HYPOTHESIS: If supported by empirical data, our model will help to interpret critical experiments addressing the relations between attention, discrimination and learning

Influence of the intracellular GluN2 C-terminal domain on NMDA receptor function

Excitatory neurotransmission mediated by N−methyl−D−aspartate receptors (NMDARs) is fundamental to learning and memory and, when impaired, causes certain neurological disorders. NMDARs are heterotetrameric complexes composed of two GluN1 [NR1] and two GluN2(A−D) [NR2(A−D)] subunits. The GluN2 subunit is responsible for subunit−specific channel activity and gating kinetics including activation (rise time), peak open probability (peak Po) and deactivation (decay time). The peak Po of recombinant NMDARs was recently described to be controlled by the extracellular GluN2 N−terminal domain (NTD). The cytoplasmic GluN2 C−terminal domain (CTD) could also be involved, because the Po of synaptic NMDARs is reduced in mice expressing C−terminally truncated GluN2 subunits. Here, we examined the role of the GluN2 cytoplasmic tail for NMDAR channel activity and gating in HEK−293 cells. C−terminal truncation of GluN2A, GluN2B or GluN2C did not change the subunit−specific rise time but accelerated the decay time of glutamate−activated currents. Furthermore, the peak Po was reduced by about 50%for GluN2A and GluN2B but not for GluN2C. These results indicated that the CTD of GluN2 has a modulating role in NMDAR gating even in the absence of interacting synaptic proteins. Reduction of peak Po and deactivation kinetics following GluN2 C−terminal truncation were reversed by re−introducing a CTD from a different GluN2 subunit. Thus, the CTDs of GluN2 subunits behave as constitutive structural elements required for normal functioning of NMDARs but are not involved in determining the subunit−specific gating properties of NMDAR

Visual neuroscience methods for marmosets: efficient receptive field mapping and head-free eye tracking

The marmoset has emerged as a promising primate model system, in particular for visual neuroscience. Many common experimental paradigms rely on head fixation and an extended period of eye fixation during the presentation of salient visual stimuli. Both of these behavioral requirements can be challenging for marmosets. Here, we present two methodological developments, each addressing one of these difficulties. First, we show that it is possible to use a standard eye tracking system without head fixation to assess visual behavior in the marmoset. Eye tracking quality from head-free animals is sufficient to obtain precise psychometric functions from a visual acuity task. Secondly, we introduce a novel method for efficient receptive field mapping that does not rely on moving stimuli but uses fast flashing annuli and wedges. We present data recorded during head-fixation in areas V1 and V6 and show that receptive field locations are readily obtained within a short period of recording time. Thus, the methodological advancements presented in this work will contribute to establish the marmoset as a valuable model in neuroscience.Significance StatementThe marmoset monkey is becoming an increasingly relevant model for biological and medical research. Here, we present two methodological advancements for visual neuroscience that are adapted to the marmoset. First, we present a head-free eye tracking protocol that is sufficiently accurate for a large variety of visual experiments. Second, we introduce an efficient technique for mapping visual receptive fields (RFs) and apply it to map RFs of neurons from the visual cortex of head-fixed marmosets. The concepts presented in this work can be easily transferred to other species. Together, this will promote diversification of the animal model landscape and solidify the contribution of marmoset research

Cortical gamma-band resonance preferentially transmits coherent input

Synchronization has been implicated in neuronal communication, but causal evidence remains indirect. We use optogenetics to generate depolarizing currents in pyramidal neurons of the cat visual cortex, emulating excitatory synaptic inputs under precise temporal control, while measuring spike output. The cortex transforms constant excitation into strong gamma-band synchronization, revealing the well-known cortical resonance. Increasing excitation with ramps increases the strength and frequency of synchronization. Slow, symmetric excitation profiles reveal hysteresis of power and frequency. White-noise input sequences enable causal analysis of network transmission, establishing that the cortical gamma-band resonance preferentially transmits coherent input components. Models composed of recurrently coupled excitatory and inhibitory units uncover a crucial role of feedback inhibition and suggest that hysteresis can arise through spike-frequency adaptation. The presented approach provides a powerful means to investigate the resonance properties of local circuits and probe how these properties transform input and shape transmission