Gradual accumulation of evidence is thought to be fundamental for decision-making, and its neural correlates have been found in multiple brain regions1–8. Here we develop a generalizable method to measure tuning curves that specify the relationship between neural responses and mentally-accumulated evidence, and apply it to distinguish the encoding of decision variables in posterior parietal cortex (PPC) and prefrontal cortex (frontal orienting fields, FOF). We recorded the firing rates of neurons in PPC and FOF from rats performing a perceptual decision-making task. Classical analyses uncovered correlates of accumulating evidence, similar to previous observations in primates and also similar across the two regions. However, tuning curve assays revealed that while the PPC encodes a graded value of the accumulating evidence, the FOF has a more categorical encoding that indicates, throughout the trial, the decision provisionally favored by the evidence accumulated so far. Contrary to current views3,5,7–9, this suggests that premotor activity in frontal cortex does not play a role in the accumulation process, but instead has a more categorical function, such as transforming accumulated evidence into a discrete choice. To causally probe the role of FOF activity, we optogenetically silenced it during different timepoints of the trial. Consistent with a role in committing to a categorical choice at the end of the evidence accumulation process, but not consistent with a role during the accumulation itself, a behavioral effect was observed only when FOF silencing occurred at the end of the perceptual stimulus. Our results place important constraints on the circuit logic of brain regions involved in decision-making.

The amygdala is essential for fear learning and expression. The central amygdala (CeA), once viewed as a passive relay between the amygdala complex and downstream fear effectors, has emerged as an active participant in fear conditioning. However, how CeA contributes to the learning and expression of fear is unclear. Here we show in mice that fear conditioning induces robust plasticity of excitatory synapses onto inhibitory neurons in the lateral subdivision of CeA (CeL). This experience-dependent plasticity is cell-specific, bidirectional, and expressed presynaptically by inputs from the lateral amygdala. In particular, preventing synaptic potentiation onto somatostatin-positive neurons impairs fear memory formation. Furthermore, activation of these neurons is necessary for fear memory recall and sufficient to drive fear responses. Our findings support a model in which the fear conditioning-induced synaptic modifications in CeL favor the activation of somatostatin-positive neurons, which inhibit CeL output thereby disinhibiting the medial subdivision of CeA and releasing fear expression.

Many models of cognition and of neural computations posit the use and estimation of prior stimulus statistics: it has long been known that working memory and perception are strongly impacted by previous sensory experience, even when that sensory history is not relevant to the current task at hand. Nevertheless, the neural mechanisms and regions of the brain that are necessary for computing and using such prior experience are unknown. Here we report that the posterior parietal cortex (PPC) is a critical locus for the representation and use of prior stimulus information. We trained rats in an auditory parametric working memory task, and found that they displayed substantial and readily quantifiable behavioural effects of sensory-stimulus history, similar to those observed in humans and monkeys. Earlier proposals that the PPC supports working memory predict that optogenetic silencing of this region would impair behaviour in our working memory task. Contrary to this prediction, we found that silencing the PPC significantly improved performance. Quantitative analyses of behaviour revealed that this improvement was due to the selective reduction of the effects of prior sensory stimuli. Electrophysiological recordings showed that PPC neurons carried far more information about the sensory stimuli of previous trials than about the stimuli of the current trial. Furthermore, for a given rat, the more information about previous trial sensory history in the neural firing rates of the PPC, the greater the behavioural effect of sensory history, suggesting a tight link between behaviour and PPC representations of stimulus history. Our results indicate that the PPC is a central component in the processing of sensory-stimulus history, and could enable further neurobiological investigation of long-standing questions regarding how perception and working memory are affected by prior sensory information.

The changes in synaptic morphology and receptor content that underlie neural plasticity are poorly understood. Here, we use a pHsensitive green fluorescent protein to tag recombinant glutamate receptors and monitor their dynamics onto dendritic spine surfaces. We show that chemically induced long-term potentiation (chemLTP) drives robust exocytosis of AMPA receptors. In contrast, the same stimulus produces a small reduction of NMDA receptors from the spine surface. chemLTP produces similar modification of small and large spines. Interestingly, during chemLTP induction, spines increase in volume before accumulation of AMPA receptors on their surface, indicating that distinct mechanisms underlie changes in morphology and receptor content.

We developed a high-throughput methodology, termed fluorescent tagging of full-length proteins (FTFLP), to analyze expression patterns and subcellular localization of Arabidopsis gene products in planta. Determination of these parameters is a logical first step in functional characterization of the approximately one-third of all known Arabidopsis genes that encode novel proteins of unknown function. Our FTFLP-based approach offers two significant advantages: first, it produces internallytagged full-length proteins that are likely to exhibit native intracellular localization, and second, it yields information about the tissue specificity of gene expression by the use of native promoters. To demonstrate how FTFLP may be used for characterization of the Arabidopsis proteome, we tagged a series of known proteins with diverse subcellular targeting patterns as well as several proteins with unknown function and unassigned subcellular localization.