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2016 ; 13
(2
): 311-24
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Selective Manipulation of Neural Circuits
#MMPMID26951545
Park HG
; Carmel JB
Neurotherapeutics
2016[Apr]; 13
(2
): 311-24
PMID26951545
show ga
Unraveling the complex network of neural circuits that form the nervous system
demands tools that can manipulate specific circuits. The recent evolution of
genetic tools to target neural circuits allows an unprecedented precision in
elucidating their function. Here we describe two general approaches for achieving
circuit specificity. The first uses the genetic identity of a cell, such as a
transcription factor unique to a circuit, to drive expression of a molecule that
can manipulate cell function. The second uses the spatial connectivity of a
circuit to achieve specificity: one genetic element is introduced at the origin
of a circuit and the other at its termination. When the two genetic elements
combine within a neuron, they can alter its function. These two general
approaches can be combined to allow manipulation of neurons with a specific
genetic identity by introducing a regulatory gene into the origin or termination
of the circuit. We consider the advantages and disadvantages of both these
general approaches with regard to specificity and efficacy of the manipulations.
We also review the genetic techniques that allow gain- and loss-of-function
within specific neural circuits. These approaches introduce light-sensitive
channels (optogenetic) or drug sensitive channels (chemogenetic) into neurons
that form specific circuits. We compare these tools with others developed for
circuit-specific manipulation and describe the advantages of each. Finally, we
discuss how these tools might be applied for identification of the neural
circuits that mediate behavior and for repair of neural connections.
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