Inbal Goshen, Edmond and Lily Safra Center for Brain Sciences (ELSC), The Hebrew University, Israel
Astrocytes, and their surprising role in memory and reward
In addition to their well characterized supportive and homeostatic
roles, pioneering studies have shown that astrocytes directly affect neuronal
activity. In recent years, groundbreaking research revealed many surprising
roles for astrocytes in modulating neuronal activity and even behavior. To
directly and specifically modulate astrocytic activity we employed a
chemogenetic approach: We expressed the Gq-coupled designer receptor hM3Dq or
the Gi-coupled designer receptor hM4Di in astrocytes, which allowed their
time-restricted activation or inhibition (respectively) by the application of
the designer drug clozapine-N-oxide (CNO).
that in-vivo, astrocytic activation enhanced memory allocation, i.e. it
increased neuronal activity in a task-specific way, only when coupled
with learning but not in home-caged mice. Furthermore, astrocytic activation
using either chemogenetic or optogenetic tools during acquisition resulted in
memory recall enhancement on the following day. On the other hand, astrocytic Gi
pathway activation during memory acquisition impairs remote, but not recent,
recall. We show that this effect is mediated by a specific disrupting of the
projection from the hippocampus to the anterior cingulate cortex by astrocytes.
What other high
brain functions can astrocytes affect? We chronically imaged dozens of CA1
astrocytes using 2-photon microscopy, in mice that ran on a linear treadmill
and proceed in a virtual environment to obtain water rewards. We find that
astrocytic activity persistently ramps towards the reward location in a
familiar environment. When the reward location was changed in the same
environment or when mice were introduced to a novel context, the ramping was
not apparent. Following additional training, as the mice were familiarized with
the new reward location or novel context, the ramping was reestablished,
suggesting that spatial modulation of astrocytic activity is experience
dependent. This is the first indication that astrocytes can encode position
related information in learnt spatial contexts, thus broadening their known
computational abilities, and their role in cognitive functions.
continuing to look for higher brain function (now – memory engrams!) in which
astrocytes are involved.
I am a faculty member at the Edmond and Lily Safra Center for Brain Sciences (ELSC) at the Hebrew University in Jerusalem. My interest in the neural basis of behavior led me to acquire a dual-Ph.D. in Neurobiology and Psychology, followed by postdoctoral training in bioengineering. I study astrocytes, and their role in the transition between recent and remote memory, and in reward signaling. I combine imaging, electrophysiological, behavioral and molecular techniques for my studies.