Norepinephrine (NE) is widely distributed throughout the brain. It modulates intrinsic currents, as well as amplitude and frequency of synaptic transmission affecting the ‘signal-to-noise ratio’ of sensory responses. In the visual cortex, α₁- and β-adrenergic receptors (AR) gate opposing effects on long-term plasticity of excitatory transmission. Whether and how NE recruits these plastic mechanisms is not clear. Here, we show that NE modulates glutamatergic inputs with different efficacies for α₁- and β-AR. As a consequence, the priming of synapses with different NE concentrations produces dose-dependent competing effects that determine the temporal window of spike-timing dependent plasticity (STDP). While a low NE concentration leads to long-term depression (LTD) over broad positive and negative delays, a high NE concentration results in bidirectional STDP restricted to very narrow intervals. These results indicate that the local availability of NE, released during emotional arousal, determines the compound modulatory effect and the output of STDP.

The stochastic resonance (SR) is a phenomenon in which adding a moderate amount of noise can improve the signal-to-noise ratio (SNR) and performance of nonlinear systems. SR occurs in all sensory modalities including the visual system in which noise can enhance contrast detection sensitivity and the perception of ambiguous figures embedded in static scenes. Here, we explored how adding background white pixel-noise to a random dot motion (RDM) stimulus produced changes in visual motion discrimination in healthy human adults. We found that, although the average reaction times remained constant, an intermediate level of noise improved the subjects' ability to discriminate motion direction in the RDM task. The psychophysical responses followed an inverted U-like function of the input noise, whereas the incorrect responses with short reaction times did not exhibit such modulation by external noise. Moreover, by applying stimulus and noisy signals to different eyes, we found that the SR phenomenon occurred presumably in the primary visual cortex, where these two signals first converge. Our results suggest that a stochastic resonance-like phenomenon mediates the improvement of visual motion perception in the RDM task.

It is assumed that the claustrum (CL) is involved in sensorimotor integration and cognitive processes. We recorded the firing activity of identified CL neurons during classical eyeblink conditioning in rabbits, using a delay paradigm in which a tone was presented as conditioned stimulus (CS), followed by a corneal air puff as unconditioned stimulus (US). Neurons were identified by their activation from motor (MC), cingulate (CC), and medial prefrontal (mPFC) cortices. CL neurons were rarely activated by single stimuli of any modality. In contrast, their firing was significantly modulated during the first sessions of paired CS/US presentations, but not in well-trained animals. Neuron firing rates did not correlate with the kinematics of conditioned responses (CRs). CL local field potentials (LFPs) changed their spectral power across learning and presented well-differentiated CL–mPFC/CL–MC network dynamics, as shown by crossfrequency spectral measurements. CL electrical stimulation did not evoke eyelid responses, even in trained animals. Silencing of synaptic transmission of CL neurons by the vINSIST method delayed the acquisition of CRs but did not affect their presentation rate. The CL plays an important role in the acquisition of associative learning, mostly in relation to the novelty of CS/US association, but not in the expression of CRs.

The mouse is receiving growing interest as a model organism for studying visual perception. However, little is known about how discrimination and learning interact to produce visual conditioned responses. Here, we adapted a two-alternative forced-choice visual discrimination task for mice and examined how training with equiprobable stimuli of varying similarity influenced conditioned response and discrimination performance as a function of learning. Our results indicate that the slope of the gradients in similarity during training determined the learning rate, the maximum performance and the threshold for successful discrimination. Moreover, the learning process obeyed an inverse relationship between discrimination performance and discriminative resolution, implying that sensitivity within a similarity range cannot be improved without sacrificing performance in another. Our study demonstrates how the interplay between discrimination and learning controls visual discrimination capacity and introduces a new training protocol with quantitative measures to study perceptual learning and visually-guided behavior in freely moving mice.

Prolonged imbalance in sensory experience leads to dramatic readjustments in cortical representation. Neuromodulatory systems play a critical role in habilitating experience-induced plasticity and regulate memory processes in vivo. Here, we show that a brief period of intense patterned visual stimulation combined with systemic activation of alpha-1 adrenergic neuromodulator receptors (α₁-ARs) leads to a rapid, reversible, and NMDAR-dependent depression of AMPAR-mediated transmission from ascending inputs to layer II/III pyramidal cells in the visual cortex of young and adult mice. The magnitude of this form of α₁-AR long-term depression (LTD), measured ex vivo with miniature EPSC recordings, is graded by the number of orientations used during visual experience. Moreover, behavioral tests of visual function following the induction of α₁-AR LTD reveal that discrimination accuracy of sinusoidal drifting gratings is selectively reduced at high spatial frequencies in a reversible, orientation-specific, and NMDAR-dependent manner. Thus, α₁-ARs enable rapid cortical synaptic depression which correlates with an orientation-specific decrease in visual discrimination. These findings contribute to our understanding of how adrenergic receptors interact with neuronal networks in response to changes in active sensory experience to produce adaptive behavior.

Animal choices depend on direct sensory information, but also on the dynamic changes in the magnitude of reward. In visual discrimination tasks, the emergence of lateral biases in the choice record from animals is often described as a behavioral artifact, because these are highly correlated with error rates affecting psychophysical measurements. Here, we hypothesized that biased choices could constitute a robust behavioral strategy to solve discrimination tasks of graded difficulty. We trained mice to swim in a two-alterative visual discrimination task with escape from water as the reward. Their prevalence of making lateral choices increased with stimulus similarity and was present in conditions of high discriminability. While lateralization occurred at the individual level, it was absent, on average, at the population level. Biased choice sequences obeyed the generalized matching law and increased task efficiency when stimulus similarity was high. A mathematical analysis revealed that strongly-biased mice used information from past rewards but not past choices to make their current choices. We also found that the amount of lateralized choices made during the first day of training predicted individual differences in the average learning behavior. This framework provides useful analysis tools to study individualized visual-learning trajectories in mice.