Fear can be acquired vicariously through social observation of others suffering from aversive stimuli. We found that mice (observers) developed freezing behavior by observing other mice (demonstrators) receive repetitive foot shocks. Observers had higher fear responses when demonstrators were socially related to themselves, such as siblings or mating partners. Inactivation of anterior cingulate cortex (ACC) and parafascicular or mediodorsal thalamic nuclei, which comprise the medial pain system representing pain affection, substantially impaired this observational fear learning, whereas inactivation of sensory thalamic nuclei had no effect. The ACC neuronal activities were increased and synchronized with those of the lateral amygdala at theta rhythm frequency during this learning. Furthermore, an ACC-limited deletion of Ca v 1.2 Ca 2+ channels in mice impaired observational fear learning and reduced behavioral pain responses. These results demonstrate the functional involvement of the affective pain system and Ca v 1.2 channels of the ACC in observational social fear.Fear is a biological response to dangerous, threatening situations or stimuli. Fear can be acquired and expressed in a variety of ways 1 . First, fear can be learned from direct experience of an adverse situation (for example, an unconditioned stimulus in classical Pavlovian fear conditioning). In a classical conditioning experiment, pairing of a neutral, conditioned stimulus (for example, a tone) with an aversive, unconditioned stimulus (for example, a foot shock) causes an animal to express fear behaviors when the animal is later exposed to the conditioned Correspondence should be addressed to H.-S.S. (shin@kist.re.kr). 6 Present address: Department of Neurology, Seoul National University Hospital, Seoul, Korea.Note: Supplementary information is available on the Nature Neuroscience website. AUTHOR CONTRIBUTIONS COMPETING FINANCIAL INTERESTSThe authors declare no competing financial interests.Reprints and permissions information is available online at http://www.nature.com/reprintsandpermissions/. 1,[6][7][8][9][10][11][12] . Previous studies using a barpressing protocol found that rats seeing a distressed conspecific (by electric shocks) display fearful behavioral responses, such as crouching or motionlessness 13,14 . A recent study found that C57BL/6J mice that observed unfamiliar mice experiencing classical fear conditioning displayed freezing behaviors when they were later exposed to the conditioned stimulus alone 15 . These findings demonstrate social transfer of fear in rodents. Unlike classical fear conditioning, however, the neural substrate and mechanism underlying observational social fear has not been well defined. NIH Public AccessACC is known to receive sensory signals from the somatosensory cortices and other cortical areas, including the anterior insular cortex [16][17][18][19][20] . Brain-imaging studies in humans have shown that the neuronal activities of the ACC and the amygdala change during observation of others experi...

While the interaction of the cardinal rhythms of non-rapid-eye-movement (NREM) sleep-the thalamo-cortical spindles, hippocampal ripples, and the cortical slow oscillations-is thought to be critical for memory consolidation during sleep, the role spindles play in this interaction is elusive. Combining optogenetics with a closed-loop stimulation approach in mice, we show here that only thalamic spindles induced in-phase with cortical slow oscillation up-states, but not out-of-phase-induced spindles, improve consolidation of hippocampus-dependent memory during sleep. Whereas optogenetically stimulated spindles were as efficient as spontaneous spindles in nesting hippocampal ripples within their excitable troughs, stimulation in-phase with the slow oscillation up-state increased spindle co-occurrence and frontal spindle-ripple co-occurrence, eventually resulting in increased triple coupling of slow oscillation-spindle-ripple events. In-phase optogenetic suppression of thalamic spindles impaired hippocampus-dependent memory. Our results suggest a causal role for thalamic sleep spindles in hippocampus-dependent memory consolidation, conveyed through triple coupling of slow oscillations, spindles, and ripples.

The generation of the mammalian heartbeat is a complex and vital function requiring multiple and coordinated ionic channel activities. The functional role of low-voltage activated (LVA) T-type calcium channels in the pacemaker activity of the sinoatrial node (SAN) is, to date, unresolved. Here we show that disruption of the gene coding for CaV3.1/alpha1G T-type calcium channels (cacna1g) abolishes T-type calcium current (I(Ca,T)) in isolated cells from the SAN and the atrioventricular node without affecting the L-type Ca2+ current (I(Ca,L)). By using telemetric electrocardiograms on unrestrained mice and intracardiac recordings, we find that cacna1g inactivation causes bradycardia and delays atrioventricular conduction without affecting the excitability of the right atrium. Consistently, no I(Ca,T) was detected in right atrium myocytes in both wild-type and CaV3.1(-/-) mice. Furthermore, inactivation of cacna1g significantly slowed the intrinsic in vivo heart rate, prolonged the SAN recovery time, and slowed pacemaker activity of individual SAN cells through a reduction of the slope of the diastolic depolarization. Our results demonstrate that CaV3.1/T-type Ca2+ channels contribute to SAN pacemaker activity and atrioventricular conduction.