Biology subjects

Novak, L.

Publications and source records attributed to Novak, L..

3 recordsLinked to original sources

bioRxiv2021

Pattern separation and tuning shift in human sensory cortex underlie fear memory

Animal research has recognized the role of the sensory cortex in fear memory and two key underlying mechanisms--pattern separation and tuning shift. We interrogated these mechanisms in the human sensory cortex in an olfactory differential conditioning study with a delayed (9-day) retention test. Combining affective appraisal and olfactory psychophysics with functional magnetic resonance imaging (fMRI) multivoxel pattern analysis and voxel-based tuning analysis over a linear odor-morphing continuum, we confirmed affective and perceptual learning and memory and demonstrated associative plasticity in the human olfactory (piriform) cortex. Specifically, the piriform cortex exhibited immediate and lasting enhancement in pattern separation (between the conditioned stimuli/CS and neighboring non-CS) and late-onset yet lasting tuning shift towards the CS, especially in anxious individuals. These findings highlight an evolutionarily conserved sensory cortical system of fear memory, which can underpin sensory encoding of fear/threat and confer a sensory mechanism to the neuropathophysiology of anxiety.

neuroscience↗

bioRxiv2021

Nontypeable Haemophilus influenzae infection impedes Pseduomonas aeruginosa colonization and persistence in mouse respiratory tract

Patients with cystic fibrosis (CF) experience lifelong respiratory infections which are a significant cause of morbidity and mortality. These infections are polymicrobial in nature, and the predominant bacterial species undergo a predictable series of changes as patients age. Young patients have populations dominated by opportunists that are typically found within the microbiome of the human nasopharynx, such as nontypeable Haemophilus influenzae (NTHi); these are eventually supplanted and the population within the CF lung is later dominated by pathogens such as Pseudomonas aeruginosa (Pa). In this study, we investigated how initial colonization with NTHi impacts colonization and persistence of Pa in the respiratory tract. Analysis of polymicrobial biofilms in vitro by confocal microscopy revealed that NTHi promoted greater levels of Pa biofilm volume and diffusion. However, sequential respiratory infection of mice with NTHi followed by Pa resulted in significantly lower Pa as compared to infection with Pa alone. Coinfected mice also had reduced airway tissue damage and lower levels of inflammatory cytokines as compared with Pa infected mice. Similar results were observed after instillation of heat-inactivated NTHi bacteria or purified NTHi lipooligosaccharide (LOS) endotoxin prior to Pa introduction. Based on these results, we conclude that NTHi significantly reduces susceptibility to subsequent Pa infection, most likely due to priming of host innate immunity rather than a direct competitive interaction between species. These findings have potential significance with regard to therapeutic management of early life infections in patients with CF.

microbiology↗

bioRxiv2017

Human olfactory cortex contributes to emotional and perceptual aspects of aversive associative learning and memory

The role of the sensory cortex, beyond the amygdala, has been increasingly recognized in animal associative learning and memory. Here, we examined olfactory cortical plasticity in human olfactory associative learning and memory, while elucidating related changes in emotional and perceptual responses. Psychophysical and neurometric analyses were conducted across an odor-morphing continuum, with the two extreme levels differentially conditioned with aversive and neutral stimuli. Conditioned odors acquired distinct emotional values, tracked by ensemble response patterns in the orbitofrontal (high-level) olfactory cortex. Also observed were enhanced perceptual discrimination and divergent ensemble neuronal response patterns in the anterior and posterior piriform (low-to-intermediate-level) olfactory cortices. Whereas emotional-learning-related changes, both behavioral and neural, maintained 8 days later, perceptual-learning-related changes, also both behavioral and neural, recovered by then, highlighting the human aptitude of forming persistent emotional memory and related sensory cortical plasticity in contrast to transient perceptual alterations of sensory stimuli associated with mild aversive experiences.

neuroscience↗