Optogenetics is Advancing into New Dimensions

Optogenetics

 Optogenetics  is an Emerging Technology in which genetically manipulated neural cells combined with a light source for selectively On/Off the areas of the brain. The method has proven in animal studies to be extremely interesting for neuroscience and could someday lead to new therapies. 

Pros and Cons in Optogenetics

So far, the necessary light rays are normally delivered only to specific points in the brain, although the brain activity consists of a complex sequence of activations in different areas.

A novel 3-D chip to the optogenetics therefore lead into the third dimension

With the possibility of Sending light patterns of nerve cells to almost anywhere in the brain.  According to Technology Review in its online edition:

“In the coming years there will be many of these devices,” says Ilker Ozden, research professor at the Nanophotonics and Neuroengineering Laboratory at Brown University, who are working on similar technologies.

The new device comes from the Synthetic Biology Group at the MIT Media Lab.

“The brain is a three-dimensional object,” explains Ed Boyden, senior author of the new study. Far more than two optical fibers were used to control parts of the nerve cells. Would be necessary here, but much more control. A single light source is as if you play only one note, says Boyden. ”A 3-D chip allows us to control the brain, such as a keyboard.”

Method

Example_of_optogenetic_activation_of_prefrontal_cortex

Fig 1. Channelrhodopsin-2 (ChR2) induces temporally precise blue light-driven activity in rat prelimbic prefrontal cortical neurons. a) In vitro schematic (left) showing blue light delivery and whole-cell patch-clamp recording of light-evoked activity from a fluorescent CaMKll?::ChR2-EYFP expressing pyramidal neuron (right) in an acute brain slice. b) In vivo schematic (left) showing blue light (473 nm) delivery and single-unit recording. (bottom left) Coronal brain slice showing expression of CaMKll?::ChR2-EYFP in the prelimbic region. Light blue arrow shows tip of the optical fiber; black arrow shows tip of the recording electrode (left). White bar, 100 microns. (bottom right) In vivo light recording of prefrontal cortical neuron in a transduced CaMKll?::ChR2-EYFP rat showing light-evoked spiking to 20 Hz delivery of blue light pulses (right). Inset, representative light-evoked single-unit response.
Cooper_laboratory_recording_of_optogenetic_silencing_of_prefrontal_cortical_neuron
Fig 2. Halorhodopsin (NpHR) rapidly and reversibly silences spontaneous activity in vivo in rat prelimbic prefrontal cortex. (Top left) Schematic showing in vivo green (532 nm) light delivery and single- unit recording of a spontaneously active CaMKll?::eNpHR3.0- EYFP expressing pyramidal neuron. (Right) Example trace showing that continuous 532 nm illumination inhibits single-unit activity in vivo. Inset, representative single unit event; Green bar, 10 seconds.

Applications

“In vivo” optogenetic activation and/or silencing has been recorded in the following brain regions and cell-types.

  • Prefrontal Cortex

In vivo and in vitro recordings (by the Cooper laboratory) of individual CAMKII AAV-ChR2 expressing pyramidal neurons within the prefrontal cortex demonstrated high fidelity action potential output with short pulses of blue light at 20 Hz (Figure 1).The same group recorded complete green light-induced silencing of spontaneous activity in the same prefrontal cortical neuronal population expressing an AAV-NpHR vector (Figure 2).

  • Nucleus Accumbens
    • Cholinergic Interneurons

The Deisseroth laboratory integrated optogenetics, freely moving mammalian behavior, “in vivo” electrophysiology, and slice physiology to probe the cholinergic interneurons of the nucleus accumbens by direct excitation or inhibition. Despite representing less than 1% of local neurons, these cholinergic cells have dominant control roles, exerting powerful modulation of circuit activity. Furthermore, these neurons are activated by cocaine, and silencing this drug-induced activity during cocaine exposure blocked cocaine conditioning suggesting an important role for these interneurons in drug reward mechanisms.

The goal is to increase the amount of information that can be processed one optogenetics system.

Still, the chip has not been tested on animals, the researchers are currently to use the device in living mice and to examine the activation patterns. .” By Using a 3-D array for optogenetics, there is a set of possibilities that you could not even think so far,” says Boyden.

Source


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