Past events

Monoaminergic (noradrenergic, dopaminergic and serotonergic) modulation of hippocampal activity is assumed to play a major role in neuronal plasticity, learning and memory. Understanding the locus of action of these neuromodulators at the cellular level will expand our knowledge of their nature and allow us to identify issues related to their dysfunction. In the present work I study the effects of norepinephrine (NE) and dopamine (DA) on spontaneous and evoked activity in patch-clamped neurons of hippocampal slices. Both DA and NE induced a significant decrease in the amplitude of the evoked PSCs recorded from CA1 pyramidal neurons in response to stimulation of the Schaffer collaterals, accompanied by a small decrease in the cell input resistance, and a small hyperpolarization. While decreasing the evoked PSCs, NE promoted an overall increase in spontaneous synaptic activity. Pharmacological assessment of these results indicated an α1 adrenergic receptor involvement in both the decrease of the amplitude of evoked PSCs as well as the increase in spontaneous activity. Surprisingly, the effect of NE on evoked PSCs was partially antagonized by D1 dopaminergic receptor antagonist SCH23390, which suggests that NE activates dopamine receptors. The effect of DA on evoked PSCs was blocked by α1 adrenergic receptor antagonist prazosin, which suggests that DA, in turn, is activating adrenergic receptors. Noradrenergic system is highly affected by stress; in particular, the differences between NE effects in dorsal and ventral hippocampus (DH and VH, respectively) have been shown to change in stressed animals. In this work I used two types of stress protocols – Prenatal Stress (PS) and Acute Stress (AS) – to study the effect of stress on monoamine responses in slices of DH and VH. In non-stressed rats, NE effect on the evoked PSCs is larger in DH than in VH. PS and AS rats increased NE effect in VH, thus abolishing the difference between DH and VH. Pharmacological data suggests that these differences result from differential efficiencies of α1 and D1 receptors between DH and VH of both control and PS rats. Acute stress reversed the difference between PS and control rats; in the AS slices the PSC reduction was significantly different between DH and VH of PS rats, and not in control rats. I conclude that stress increases the NE modulation in VH, but not in DH, thus increasing the role of emotional processing associated with the VH.

In my PhD I led three projects probing human behavioral and physiological responses to olfactory stimuli in health and disease. In these projects I used every-day olfactory occurrences in order to infer on biological underpinnings of human behavior. In my main project I tested olfactory processing in autism, using the sniff response, a ten-minute non-verbal measure of respiratory response to odors. I found this objective measure to be profoundly altered in children with autism, and furthermore, to be highly correlated with autism severity. Using computational methods, I demonstrated 81% correct ASD classification based on differences in olfactory processing alone. These results provide proof-of-concept for a potential biomarker for autism (Rozenkrantz et al, Curr Bio, 2015). In a second and soon-to-be-submitted project, I investigated olfactory social communication in recurrent pregnancy loss (RPL), resting on a phenomenon in rodents in which females miscarry following exposure to bodily odors of non-stud males. I found that women with RPL display heightened social olfactory abilities, which were significantly correlated with number of miscarriages. Additionally, women with RPL showed significantly altered hormonal, physiological and neural responses to body odors of unfamiliar men. This project provides novel evidence for altered olfactory processing in human recurrent miscarriages. The third project is also my first foothold in placebo effect research, which I will pursue in my postdoc. Taking advantage of the non-invasive nature of olfactory stimuli, I used an odor as the placebo carrier, and tested two groups of subjects for different creativity tests. Both groups smelled the odor, but only the placebo group was told that it increases creativity (placebo manipulation). I found that following this simple manipulation, the placebo group displayed significantly enhanced creativity (Rozenkrantz et al., PLoS one, 2017). Taken together, these projects convey my deep interest in the interplay between human behavior and physiology.

A specific motor action can lead to different sensory consequences, and a particular sensory consequence can be achieved by different motor actions. This non-unique mapping between actions and sensory consequences is context dependent and requires learning in order to optimize behavior. During my talk, I will describe behavioral and neuroimaging studies in humans, in which we examined how actions modulate perception and how perception can lead to motor skill learning even in the absence of voluntary movement. Manipulating the link between actions and their sensory consequences by using virtual reality, we explore various training techniques to facilitate learning in healthy subjects and rehabilitation in patients with hemiparesis due to neurological origin.