The representation of contextual fear memories evolves over time in the hippocampus, amygdala, and prefrontal cortex.

Hyperactivity within the ventral hippocampus (vHPC) has been linked to both psychosis in humans and behavioral deficits in animal models of schizophrenia. A local decrease in GABA-mediated inhibition, particularly involving parvalbumin (PV)-expressing GABA neurons, has been proposed as a key mechanism underlying this hyperactive state. However, direct evidence is lacking for a causal role of vHPC GABA neurons in behaviors associated with schizophrenia. Here, we probed the behavioral function of two different but overlapping populations of vHPC GABA neurons that express either PV or GAD65 by selectively inhibiting these neurons with the pharmacogenetic neuromodulator hM4D. We show that acute inhibition of vHPC GABA neurons in adult mice results in behavioral changes relevant to schizophrenia. Inhibiting either PV or GAD65 neurons produced distinct behavioral deficits. Inhibition of PV neurons, affecting ∼80% of the PV neuron population, robustly impaired prepulse inhibition of the acoustic startle reflex (PPI), startle reactivity, and spontaneous alternation, but did not affect locomotor activity. In contrast, inhibiting a heterogeneous population of GAD65 neurons, affecting ∼40% of PV neurons and 65% of cholecystokinin neurons, increased spontaneous and amphetamine-induced locomotor activity and reduced spontaneous alternation, but did not alter PPI. Inhibition of PV or GAD65 neurons also produced distinct changes in network oscillatory activity in the vHPCin vivo. Together, these findings establish a causal role for vHPC GABA neurons in controlling behaviors relevant to schizophrenia and suggest a functional dissociation between the GABAergic mechanisms involved in hippocampal modulation of sensorimotor processes.

Anatomical connectivity and single neuron coding suggest a segregation of information representation within lateral (LEC) and medial (MEC) portions of the entorhinal cortex, a brain region serving as the primary input/output of the hippocampus and maintaining widespread connections to many association cortices. The present study aimed to expand this idea by examining whether these two subregions differentially contribute to memory retrieval for an association between temporally discontiguous stimuli. We found that reversible inactivation of the LEC, but not the MEC, severely impaired the retrieval of the recently and remotely acquired memory in rat trace eyeblink conditioning, in which a stimulus-free interval was interposed between the conditioned and unconditioned stimulus. Conversely, inactivation of the LEC had no effect on retrieval in delay eyeblink conditioning, where two stimuli were presented without an interval. Therefore, the LEC, but not the MEC, plays a long-lasting role in the retrieval of a memory for an association between temporally discontiguous stimuli.

Memories for recent experiences are rich in incidental detail, but with time the brain is thought to extract latent rules and structures common across past experiences. We show that over weeks following the acquisition of two distinct associative memories, neuron firing in the rat prelimbic prefrontal cortex (mPFC) became less selective for perceptual features unique to each association and, with an apparently different time-course, became more selective for common relational features. We further found that during exposure to a novel experimental context, memory expression and neuron selectivity for relational features immediately generalized to the new situation. These neural patterns offer a window into the network-level processes by which the mPFC develops a knowledge structure of the world that can be adaptively applied to new experiences.

The facial width-to-height ratio, a size-independent sexually dimorphic property of the human face, is correlated with aggressive behaviour in men. Furthermore, observers' estimates of aggression from emotionally neutral faces are accurate and are highly correlated with the facial width-to-height ratio. We investigated whether observers use the facial width-to-height ratio to estimate propensity for aggression. In experiments 1a–1c, estimates of aggression remained accurate when faces were blurred or cropped, manipulations that reduce featural cues but maintain the facial width-to-height ratio. Accuracy decreased when faces were scrambled, a manipulation that retains featural information but disrupts the facial width-to-height ratio. In experiment 2, computer-modeling software identified eight facial metrics that correlated with estimates of aggression; regression analyses revealed that the facial width-to-height ratio was the only metric that uniquely predicted these estimates. In experiment 3, we used a computer-generated set of faces varying in perceived threat (Oosterhof and Todorov, 2008 Proceedings of the National Academy of Sciences of the USA 105 11087–11092) and found that as emotionally neutral faces became more ‘threatening’, the facial width-to-height ratio increased. Together, these experiments suggest that the facial width-to-height ratio is an honest signal of propensity for aggressive behaviour.