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1.  Central cholinergic neurons are rapidly recruited by reinforcement feedback 
Cell  2015;162(5):1155-1168.
Basal forebrain cholinergic neurons constitute a major neuromodulatory system implicated in normal cognition and neurodegenerative dementias. Cholinergic projections densely innervate neocortex, releasing acetylcholine to regulate arousal, attention and learning. However, their precise behavioral function is poorly understood because identified cholinergic neurons have never been recorded during behavior. To determine which aspects of cognition their activity might support we recorded cholinergic neurons using optogenetic identification in mice performing an auditory detection task requiring sustained attention. We found that a non-cholinergic basal forebrain population — but not cholinergic neurons — were correlated with trial-to-trial measures of attention. Surprisingly, cholinergic neurons responded to reward and punishment with unusual speed and precision (18±3ms). Cholinergic responses were scaled by the unexpectedness of reinforcement and were highly similar across neurons and two nuclei innervating distinct cortical areas. These results reveal that the cholinergic system broadcasts a rapid and precisely timed reinforcement signal supporting fast cortical activation and plasticity.
PMCID: PMC4833212  PMID: 26317475
basal forebrain; nucleus basalis; neuromodulation; reward; punishment; surprise
2.  Avian scavengers and the threat from veterinary pharmaceuticals 
Veterinary use of the non-steroidal anti-inflammatory drug diclofenac on domesticated ungulates caused populations of resident Gyps vultures in the Indian sub-continent to collapse. The birds died when they fed on carrion from treated animals. Veterinary diclofenac was banned in 2006 and meloxicam was advocated as a ‘vulture-safe’ alternative. We examine the effectiveness of the 2006 ban, whether meloxicam has replaced diclofenac, and the impact of these changes on vultures. Drug residue data from liver samples collected from ungulate carcasses in India since 2004 demonstrate that the prevalence of diclofenac in carcasses in 2009 was half of that before the ban and meloxicam prevalence increased by 44%. The expected vulture death rate from diclofenac per meal in 2009 was one-third of that before the ban. Surveys at veterinary clinics show that diclofenac use in India began in 1994, coinciding with the onset of rapid Gyps declines ascertained from measured rates of declines. Our study shows that one pharmaceutical product has had a devastating impact on Asia's vultures. Large-scale research and survey were needed to detect, diagnose and quantify the problem and measure the response to remedial actions. Given these difficulties, other effects of pharmaceuticals in the environment may remain undetected.
PMCID: PMC4213586  PMID: 25405963
non-steroidal anti-inflammatory drugs; Gyps vultures; diclofenac; meloxicam; scavengers; pharmaceuticals
3.  From circuit motifs to computations: mapping the behavioral repertoire of cortical interneurons 
The exquisite architecture of cortex incorporates a myriad of inhibitory interneuron types. Until recently, the dearth of techniques for cell type identification in awake animals has made it difficult to link interneuron activity with circuit function, computation and behavior. This situation has changed dramatically in recent years with the advent of novel tools for targeting genetically distinct interneuron types so their activity can be observed and manipulated. The association of different interneuron subtypes with specific circuit functions, such as gain modulation or disinhibition, is starting to reveal canonical circuit motifs conserved across neocortical regions. Moreover, it appears that some interneuron types are recruited at specific behavioral events and likely control the flow of information among and within brain areas at behavioral time scales. Based on these results we propose that interneuron function goes beyond network coordination and interneurons should be viewed as integral elements of cortical computations serving behavior.
PMCID: PMC4090079  PMID: 24508565
4.  Multiple modes of phase locking between sniffing and whisking during active exploration 
Sense organs are often actively controlled by motor processes and such active sensing profoundly shapes the timing of sensory information flow. The temporal coordination between different active sensing processes is less well understood but is essential for multisensory integration, coordination between brain regions, and energetically optimal sampling strategies. Here we studied the coordination between sniffing and whisking, the motor processes in rodents that control the acquisition of smell and touch information, respectively. Sniffing, high frequency respiratory bouts, and whisking, rapid back and forth movements of mystacial whiskers, occur in the same theta frequency range (4-12 Hz) leading to a hypothesis that these sensorimotor rhythms are phase-locked. To test this, we monitored sniffing using a thermocouple in the nasal cavity and whisking with an electromyogram (EMG) of the mystacial pad in rats engaged in an open field reward foraging behavior. During bouts of exploration, sniffing and whisking showed strong one-to-one phase-locking within the theta frequency range (4-12 Hz). Interestingly, we also observed multi-mode phase-locking with multiple whisks within a sniff cycle or multiple sniffs within a whisk cycle – always at the same preferred phase. This specific phase relationship coupled the acquisition phases of the two sensorimotor rhythms, inhalation and whisker protraction. Our results suggest that sniffing and whisking may be under the control of interdependent rhythm generators that dynamically coordinate active acquisition of olfactory and somatosensory information.
PMCID: PMC3785235  PMID: 23658164
sensorimotor rhythms; active sensing; theta; coherence; multisensory; foraging
5.  The Population Decline of Gyps Vultures in India and Nepal Has Slowed since Veterinary Use of Diclofenac was Banned 
PLoS ONE  2012;7(11):e49118.
Populations of oriental white-backed vulture (Gyps bengalensis), long-billed vulture (Gyps indicus) and slender-billed vulture (Gyps tenuirostris) crashed during the mid-1990s throughout the Indian subcontinent. Surveys in India, initially conducted in 1991–1993 and repeated in 2000, 2002, 2003 and 2007, revealed that the population of Gyps bengalensis had fallen by 2007 to 0.1% of its numbers in the early 1990s, with the population of Gyps indicus and G. tenuirostris combined having fallen to 3.2% of its earlier level. A survey of G. bengalensis in western Nepal indicated that the size of the population in 2009 was 25% of that in 2002. In this paper, repeat surveys conducted in 2011 were analysed to estimate recent population trends. Populations of all three species of vulture remained at a low level, but the decline had slowed and may even have reversed for G. bengalensis, both in India and Nepal. However, estimates of the most recent population trends are imprecise, so it is possible that declines may be continuing, though at a significantly slower rate. The degree to which the decline of G. bengalensis in India has slowed is consistent with the expected effects on population trend of a measured change in the level of contamination of ungulate carcasses with the drug diclofenac, which is toxic to vultures, following a ban on its veterinary use in 2006. The most recent available information indicates that the elimination of diclofenac from the vultures’ food supply is incomplete, so further efforts are required to fully implement the ban.
PMCID: PMC3492300  PMID: 23145090
6.  Sparse optical microstimulation in barrel cortex drives learned behaviour in freely moving mice 
Nature  2008;451(7174):61-64.
Electrical microstimulation can establish causal links between the activity of groups of neurons and perceptual and cognitive functions 1–6. However, the number and identities of neurons microstimulated, as well as the number of action potentials evoked, are difficult to ascertain 7, 8. To address these issues we introduced the light-gated algal channel channelrhodopsin-2 (ChR2) 9 specifically into a small fraction of layer 2/3 neurons of the mouse primary somatosensory cortex. ChR2 photostimulation in vivo reliably generated stimulus-locked action potentials 10–13 at frequencies up to 50 Hz. Naïve mice readily learned to detect brief trains of action potentials (5 light pulses, 1ms, 20 Hz). After training, mice could detect a photostimulus firing a single action potential in approximately 300 neurons. Even fewer neurons (approximately 60) were required for longer stimuli (5 action potentials, 250 ms). Our results show that perceptual decisions and learning can be driven by extremely brief epochs of cortical activity in a sparse subset of supragranular cortical pyramidal neurons.
PMCID: PMC3425380  PMID: 18094685
7.  Patterns in abundance and diversity of faecally dispersed parasites of tiger in Tadoba National Park, central India 
BMC Ecology  2002;2:6.
Importance of parasites in ecological and evolutionary interactions is being increasingly recognized. However, ecological data on parasites of important host species is still scanty. We analyze the patterns seen in the faecal parasites of tigers in the Tadoba National Park, India, and speculate on the factors and processes shaping the parasite community and the possible implications for tiger ecology.
The prevalence and intensities were high and the parasite community was dominated by indirect life cycle parasites. Across all genera of parasites variance scaled with the square of the mean and there was a significant positive correlation between prevalence and abundance. There was no significant association between different types of parasites.
The 70 samples analyzed formed 14 distinct clusters. If we assume each of the clusters to represent individual tigers that were sampled repeatedly and that resident tigers are more likely to be sampled repeatedly, the presumed transient tigers had significantly greater parasite loads than the presumed resident ones.
PMCID: PMC111199  PMID: 12000685

Results 1-7 (7)