Symposium – Behaviour and neural circuits

S11-01

Neural circuit formation in zebrafish

Michael Granato

University of Pennsylvania, Philadelphia, United States

Whole animal behaviors require precise wiring of the nervous

system. Yet how neuronal wiring translates into defined behaviors

is not well understood. To study the interplay between nervous

system development and behavior, we focus on neuronal wiring

(axonal guidance and synapse formation) controlling defined

motor behaviors. In genetic screens for motor axon guidance

and synapse formation, we have identified a series of genes that

have allowed us to dissect at the molecular and cellular level

how motor axons navigate from the spinal cord to their muscle

targets, and how they form the first neuromuscular synapses [1–

3]. In parallel, we have conducted genetic screens to identify genes

controlling the modulation of motor behaviors. We have focused

on the startle response, which is a evolutionary conserved and

well-characterized motor behavior modulated by sensory stimuli.

For example, the display of a sub-threshold stimulus (i.e. a stimu-

lus too weak to elicit a response on its own) just prior to a startling

stimulus, suppresses the startle response through neural process-

ing called sensorimotor gating. Despite its importance (patients

with schizophrenia have severe sensorimotor deficits) the molec-

ular and cellular pathways underlying sensorimotor are not very

well understood. We have recently established the zebrafish as a

model to study sensorimotor gating, and in a genetic screen we

have identified several mutants with specific defects in this pro-

cess [4]. We will discuss our ongoing efforts to integrate neuronal

wiring (axonal guidance and synapse formation) during develop-

ment with the function of neural circuits controlling defined

motor behaviors (sensorimotor gating, phototaxis).

doi:10.1016/j.mod.2009.06.1029

S11-02

Activity and signalling in the development of neural morphology

and locomotion

Ajeet P. Singh1, Sudhir P. Pallayil2, B.M. Shweta2, Akila Sridhar2,

Veronica Rodrigues1,2, K. VijayRaghavan2

1Tata Institute of Fundamental Research, Mumbai, India2National Centre for Biological Sciences, Bangalore, India

In trying to understand how neural networks develop, work

has largely focused on identifying mechanisms that specify the

cell fate and morphogenesis of each unit followed by efforts to

decipher how these units are connected. These studies have been

invaluable in providing us an understanding of how the anatomy

or the ‘form’ of neural networks are put in place. We know much

less about how this form relates to the development of function.

We are at very early stages in our attempts to integrate an under-

standing of how neuronal form, physiology and connectivity are

related to the development of coordinated locomotion. Using an

identified neuron, I will begin by briefly summarizing how activity

and Wnt signalling pathways act together to develop neuronal

arbors. Next, using the adult motor system of Drosophila as an

example, I will summarize progress on how activity and signal-

ling pathways work to control the development of adult walking

behaviour.

doi:10.1016/j.mod.2009.06.1030

S11-03

Serotonergic neurogenesis from a bipotent progenitor pool serves

as a model for the coordination of neuronal birth order and

identity by intrinsic genetic programs

John Jacob1,2, Robert Storm3, Diogo Castro1, Chris Milton1,

Patrick Pla4, Francois Guillemot1, Siew-Lan Ang1,

Carmen Birchmeier3, James Briscoe1

1MRC National Institute for Medical Research, London, United Kingdom2National Hospital for Neurology and Neurosurgery, London, United

Kingdom3Max-Delbruck-Centrum for Molecular Medicine, Berlin, Germany4Ecole Normale Superieure, Paris, France

Birth order is linked to neuronal identity in many regions of

the central nervous system. However the mechanisms that

underpin this temporal phenomenon are poorly understood. A

tractable system to investigate this problem is the ventral hind-

brain, where two physiologically important neuronal subtypes,

visceral motor (VM) and serotonergic (5HT) neurons are derived

sequentially from a common progenitor pool. Previous studies

have implicated intrinsic determinants in the specification of

either subtype. Here we address how intrinsic factors expressed

in progenitors coordinate this stereotyped temporal fate switch,

and their involvement in the elaboration of serotonergic neuronal

identity. Our recent studies have shown that the temporal fate

switch is activated through sequential cross-repression between

the forkhead transcription factor, Foxa2 and the VM determinant,

Phox2b. These findings suggest that cross-repression is a funda-

mental regulatory motif in the generation of neuronal diversity

in space and time. During the subsequent elaboration of neuronal

M E C H A N I S M S O F D E V E L O P M E N T 1 2 6 ( 2 0 0 9 ) S 3 8 – S 3 9

ava i lab le at www.sc iencedi rec t .com

journal homepage: www.elsevier .com/ locate /modo

identity, the selection of neurotransmitter identity is arguably the

most important trait. Serotonin signalling regulates numerous

behaviours and abnormalities in serotonergic transmission are

implicated in several highly prevalent neurological and psychiat-

ric disorders. Using a mouse genetic approach, we demonstrate

that the progenitor-expressed transcription factor, Ascl1 partici-

pates in a feedforward circuit with the zinc-finger gene, Insm1

in the regulation of the key rate-limiting enzyme of serotonin bio-

synthesis, Tph2. Moreover, we demonstrate biochemically and

genetically that Ascl1 is a critical and direct regulator of Insm1.

These data begin to shed light on the mechanism that links neu-

ronal birth order to the acquisition of neuronal identity.

doi:10.1016/j.mod.2009.06.1031

S11-05

Neural coding of behaviors in Caenorhabitis elegans

Ikue Mori

Nagoya University, Nagoya, Japan

Thermotaxis of Caenorhabitis elegans is an ideal system for

comprehensively understanding how a neural circuit generates

a memory-regulated behavior. In our neural circuit model,

temperature is sensed and memorized by AFD and AWC sensory

neurons, neural information from AFD and AWC is conveyed to

AIY interneuron, and the subsequent information from AIY is

further conveyed to AIZ and RIA interneurons for integrating

thermal signal with feeding-state information. Expressions of

vesicular glutamate transporter EAT-4 in AFD, AWC and RIA

are required for thermotaxis. In addition, expression of chloride

channel type inhibitory glutamate receptor GLC-3 in AIY of the

glc-3 mutant restored normal thermotaxis. Thus, AIY could be

inactivated by GLC-3 upon glutamate release from either AFD

or AWC. Investigation of how AIY could discriminate glutamate

signals from AFD and AWC is underway. To obtain molecular

physiological insight onto neural computation in the circuit,

we employed light-activated ion channels, NpHR/halorhodopsin

and channelrhodopsin, to induce temporal inactivation and acti-

vation of target neuron, respectively. So far, excitation of NpHR

in AFD of wild-type animal induced abnormal migration to

higher temperature than the cultivation temperature on a ther-

mal gradient. This thermophilic abnormity is opposite to cryo-

philic abnormality observed in the animals lacking AFD or AIY.

Although ablation of AFD in wild-type animal strongly reduced

calcium influx in AIY, our calcium imaging analysis revealed

that thermal response of AIY was notably enhanced by excita-

tion of NpHR in AFD, despite thermal response of AFD itself

was partially reduced. Thus, diverse reduction level of AFD

activity may dynamically affect active and inactive states of

AIY, which as a consequence controls thermophilic and cryo-

philic migrations.

doi:10.1016/j.mod.2009.06.1032

S39M E C H A N I S M S O F D E V E L O P M E N T 1 2 6 ( 2 0 0 9 ) S 3 8 – S 3 9