COVID-19 has spread to most countries in the world. Puzzlingly, the impact of the disease is different in different countries. These differences are attributed to differences in cultural norms, mitigation efforts, and health infrastructure. Here we propose that national differences in COVID-19 impact could be partially explained by the different national policies respect to Bacillus Calmette-Guérin (BCG) childhood vaccination. BCG vaccination has been reported to offer broad protection to respiratory infections. We compared large number of countries BCG vaccination policies with the morbidity and mortality for COVID-19. We found that countries without universal policies of BCG vaccination (Italy, Nederland, USA) have been more severely affected compared to countries with universal and long-standing BCG policies. Countries that have a late start of universal BCG policy (Iran, 1984) had high mortality, consistent with the idea that BCG protects the vaccinated elderly population. We also found that BCG vaccination also reduced the number of reported COVID-19 cases in a country. The combination of reduced morbidity and mortality makes BCG vaccination a potential new tool in the fight against COVID-19.
Although systems involved in attentional selection have been studied extensively, much less is known about non-selective systems. To study these preparatory mechanisms, we compared activity in auditory cortex elicited by sounds while rats performed an auditory task (“engaged”) with activity elicited by identical stimuli while subjects were awake but not performing a task (“passive”). Surprisingly, we found that engagement suppressed responses, an effect opposite in sign to that elicited by selective attention. In the auditory thalamus, however, engagement enhanced spontaneous firing rates but did not affect evoked responses. These results demonstrate that in auditory cortex, neural activity cannot be viewed simply as a limited resource allocated in greater measure as the state of the animal passes from somnolent to passively listening to engaged and attentive. Instead the engaged condition possesses a characteristic and distinct neural signature in which sound-evoked responses are paradoxically suppressed.
The olfactory bulb receives rich glutamatergic projections from the piriform cortex. However, the dynamics and importance of these feedback signals remain unknown. Here, we use multiphoton calcium imaging to monitor cortical feedback in the olfactory bulb of awake mice and further probe its impact on the bulb output. Responses of feedback boutons were sparse, odor specific, and often outlasted stimuli by several seconds. Odor presentation either enhanced or suppressed the activity of boutons. However, any given bouton responded with stereotypic polarity across multiple odors, preferring either enhancement or suppression. Feedback representations were locally diverse and differed in dynamics across bulb layers. Inactivation of piriform cortex increased odor responsiveness and pairwise similarity of mitral cells but had little impact on tufted cells. We propose that cortical feedback differentially impacts these two output channels of the bulb by specifically decorrelating mitral cell responses to enable odor separation.
Neurons in the auditory cortex can lock with millisecond precision to the fine timing of acoustic stimuli, but it is not known whether this precise spike timing can be used to guide decisions. We used chronically implanted microelectrode pairs to stimulate neurons in the rat auditory cortex directly. Here we demonstrate that rats can exploit differences in the timing of cortical activity as short as three milliseconds to guide decisions.
Neurons in the auditory cortex can lock with millisecond precision to the fine timing of acoustic stimuli, but it is not known whether this precise spike timing can be used to guide decisions. We used chronically implanted microelectrode pairs to stimulate neurons in the rat auditory cortex directly. Here we demonstrate that rats can exploit differences in the timing of cortical activity as short as three milliseconds to guide decisions.Animals can detect the fine timing of some stimuli. For example, interaural time differences of less than one millisecond are used for the spatial localization of sound 1 . It is also clear that cortical neurons can lock with millisecond precision to the fine timing of some stimuli in the auditory cortex 2, 3 , the visual cortex 4 , somatosensory cortex 5,6 and in vitro 7 . Furthermore, spike generation in the auditory cortex is controlled by a stereotyped and precisely timed sequence of excitatory input followed approximately three milliseconds later by inhibitory input 8 . However, although it has recently been established that even a few cortical spikes are sufficient to drive decisions 9,10 , it has been difficult to establish whether the fine timing of cortical activity can suffice.We therefore set out to probe the precision with which the fine timing of neural activity in the auditory cortex could guide behaviour in the rat. For the spatial localization of sound, the relevant sub-millisecond interaural time difference cues are extracted by specialized subcortical structures. To ensure that we were probing cortical rather than subcortical mechanisms, we bypassed subcortical auditory pathways and trained animals to respond to direct intracortical electrical stimulation. We used transient biphasic current trains delivered via two chronically implanted intracortical microelectrodes 11-13 to stimulate two populations of neurons in primary auditory cortex (area A1; Fig. 1a). We designed the stimulation patterns so that the only cue available to guide behaviour was the relative timing of the activity elicited in the two cortical populations.We first trained adult male Long Evans rats to perform a simple auditory two alternative choice task (2-AC) 14 . The animal initiated a trial by inserting its nose into the centre port of a three port operant chamber, triggering one of two acoustic stimuli. These stimuli indicated whether the left or right goal port would be rewarded with water ( Fig. 1A; for details, see Supplemental material). Chance performance was 50%. After animals reached criterion performance (> 90%), we implanted electrodes at two sites (A and B; Fig. 1A) about 1.1 mm apart along the rostro-caudal axis in the rat's left primary auditory cortex (Fig. S3). We then substituted electrical stimulation (< 30 µA) through these
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