Weizmann’s 1st Zuckerman Scholar has new answers to the age-old question 

Neurobiologist Dr. Ivo Spiegel arrived on campus in May, the first Zuckerman Scholar to join the Weizmann Institute as a new tenure-track scientist. Mortimer B. Zuckerman Scholars Program in STEM Leadership was kicked off last January with a gift of $100 million from American business leader and philanthropist Mortimer B. Zuckerman, with a goal to cultivate deeper scientific ties between North America and Israel.

The gift, which is split evenly between four Israeli institutions of higher learning including the Weizmann Institute, funds postdoctoral fellows from the U.S., Canada, and other Western countries during their fellowship periods in Israel; and the recruitment of top Israeli scholars like Dr. Spiegel from abroad to join the faculties of the Israeli institutions, enabling the Israeli institutions to effectively compete with top North American institutions for the best candidates.

The other participating institutions are the Technion—Israel Institute of Technology, Tel Aviv University, and the Hebrew University of Jerusalem.

Dr. Spiegel’s research avenue will address an age-old quandary in brain science that has vast implications for the understanding of the human brain:To what extent do experience and environment dictate brain function, and to what extent do our genes do so?

The cortex, a brain area responsible for sensory processing and memory storage, is home to a diverse population of neurons, each with its own distinct function in the circuit. Excitatory neurons receive electric input and generate a stimulating output for connected neurons. Inhibitory neurons do the exact opposite: They transmit to their connected neurons a signal that is inhibitory as it opposes the currents coming from the excitatory neurons.

Thus, whether a given neuron will or will not send an electric signal to the next neuron is determined by the amount of excitation and inhibition that it receives. The tight control over this balance between the amounts of excitation and inhibition (“E/I Balance”) in the face of changing sensory experiences is critically important for normal brain function. It is achieved by regulating the sites through which neurons connect to each other to transmit information, the synapses. Genetic mutations that affect synapses and lead to changes in E/I balance were recently linked to psychiatric disorders such as autism and schizophrenia.

This E/I balance maintained by the brain is the focus of Dr. Spiegel’s work, and he is making key inroads on understanding its importance in brain function in health and in disease—specifically, to what extent genes and to what extent environmental factors affect the balance.

Dr. Spiegel received his BSc in biology with honors from Tel Aviv University, and then moved to the Weizmann Institute, where he received his MSc in 2001 and his PhD in 2007.

During his postdoctoral training at Harvard Medical School, he began to explore the molecular components underlying this delicate balancing mechanism and its effect on brain function and health. In the course of his fellowship, he identified a feature (a so-called “transcriptional program”) embedded in the genome that regulates the amount of excitation and inhibition impinging onto a given neuron—and thus helps maintain regular brain function. Each type of neuron responds to sensory stimulation by activating a unique transcriptional program, which modifies the synapses onto this neuron and thereby the function of the circuit.

Dr. Spiegel also identified a number of so-called “secreted growth factors” that are expressed in subsets of cortical neurons when a person has a sensory experience. These growth factors, he found, play a critical role in adapting the neural circuits tasked with specific behaviors to experiences.

In his new lab at the Weizmann Institute, Dr. Spiegel will continue to investigate the inner mechanics underlying the E/I-balance. In this way, he hopes to identify the mechanisms responsible for various psychiatric diseases and how our internal, emotional states regulate brain function.

 

Dr. Ivo Spiegel is supported by the Lulu P. & David J. Levidow Fund for Alzheimers Diseases and Neuroscience Research, the Honorable William Marovitz, and the Mortimer B. Zuckerman Scholars Program in STEM Leadership. Dr. Spiegel is the incumbent of the Friends of Richard and Linda Price Career Development Chair.

Dr. Ivo Spiegel on nature vs. nurture