Dr. Yair Manor: Research Interests


The effect of Neuromodulation on synaptic dynamics and network output

Animals need to shape their behavior according to internal and external factors. Neuronal networks that produce behavioral output are normally under the influence of projection neurons located in high centers. These projection neurons release neuromodulatory substances that modify the activity of the neuronal networks. Neuromodulators alter both the intrinsic properties of neurons, as well as the properties of synapses that connects these neurons. In this project we try to correlate the effects of neuromodulation on the dynamical properties of individual synapses (time course of activation, time course of depression, maximal efficacy, etc.) and on the whole neuronal network. Our experimental preparation is the stomatogastric nervous system of the lobster Homarus americanus.

This project is in collaboration with Dr. Farzan Nadim at the New Jersey Institute of Technology.

Coordination of rhythmic networks

Coordination of several motor rhythms is an extremely important task for normal function. An example for an obligatory interaction of two motor rhythms is locomotion and breathing. For efficient performance, these two functions need to be precisely coordinated in time. A good experimental model to study the mechanisms underlying the coordination of different motor rhythms is the stomatogastric ganglion of the crab Cancer borealis, where two motor rhythms are normally produced: the fast pyloric rhythm and the slow gastric mill rhythm. Each of these rhythms is produced by a small number of distinct neurons. In a recent modellng and electrophysiological study, we found that the pyloric and gastric mill rhythms are coupled through a single synaptic connection. According to the behavioral context, these two rhythms need to be coupled and uncoupled in a dynamic fashion. Neuromodulation plays an important role for this task. One of the interesting questions is how neuromodulation that acts on the pyloric neurons affect the gastric mill neurons, through the synapse that connects the two rhythms.

To study this question, we use a novel method called dynamic clamp: a computer continuously acquires the voltage of a neuron. Based on this voltage and a mathematical model that represents a dynamical conductance, the computer calculates (in real time) a current that mimics the activity of the conductance. This current is then intra-cellularly injected into the neuron. The on-line interaction between a computer and a biological preparation allows one to incorporate artificial conductances into neuron. We use this method to connect neurons with artificial synapses. Our experimental approach is to use two preparations. In preparation #1, the pyloric neurons are eliminated. In preparation #2, the gastric mill neurons are killed. With the dynamic clamp method, the gastric mill neurons in preparation #1 are artificially connected to the pyloric neurons in preparation #2. The effects of neuromodulation are then investigated separately for each preparation. This allows us to isolate the effects of the neuromodulator on the two rhythms.

This project is in collaboration with Prof. Michael Nusbaum at the University of Pennsylvania School of Medicine and Dr. Farzan Nadim at New Jersey Institute of Technology.

The role of synaptic depression in shaping the output of neuronal networks

Synaptic dynamics, such as synaptic depression or synaptic facilitation, are important elements in shaping the output of a neuronal network. A relatively simple process such as synaptic depression can have significant and unexpected actions when it is found in networks of oscillating neurons that are connected with recurrent feedback connections. Traditionally, a depressing synapse was viewed as a weak synapse, that can be made transiently strong by interrupting its activity and allowing it to recover from depression. In a recent modeling study, we found that synaptic depression incorporated in a feedback network can produce an amplification mechanism which results in a permanent strenghtenning of the synapse. Consequently, a small change in the dynamical properties of a synapse, for example through neuromodulation, can lead to a large change in the output of the network. We are currently investigating whether such amplification mechanisms exist in the pyloric network of the lobster (Panulirus interruptus) stomatogastric ganglion.

This project is in collaboration with Dr. Farzan Nadim at New Jersey Institute of Technology.

The mechanism of subthreshold oscillations in the inferior olive

The inferior olivary neurons produce subthreshold oscillations (STOs) that are involved in motor coordination. Olivary neurons are electrically coupled in mature rats. The time of gap junction formation coincides with the time at which the STOs appear. We developed a model that suggests that the subthreshold oscillation are generated as a result of electrical coupling of cells with heterogeneous properties, namely the ratio of maximal conductances. We use the dynamic clamp method to electrically couple neurons of different combinations of leak and calcium currents.

This project is in collaboration with Prof. Yosi Yarom at the Hebrew University.


Last Updated: 20/12/2005