The ability to learn associations between events is critical for survival, but it has not been clear how different pieces of information stored in memory may be linked together by populations of neurons. In a study published April 2nd in Cell Reports, synchronous activation of distinct neuronal ensembles caused mice to artificially associate the memory of a foot shock with the unrelated memory of exploring a safe environment, triggering an increase in fear-related behavior when the mice were re-exposed to the non-threatening environment. The findings suggest that co-activated cell ensembles become wired together to link two distinct memories that were previously stored independently in the brain.
“Memory is the basis of all higher brain functions, including consciousness, and it also plays an important role in psychiatric diseases such as post-traumatic stress disorder,” says senior study author Kaoru Inokuchi of the University of Toyama. “By showing how the brain associates different types of information to generate a qualitatively new memory that leads to enduring changes in behavior, our findings could have important implications for the treatment of these debilitating conditions.”
Recent studies have shown that subpopulations of neurons activated during learning are reactivated during subsequent memory retrieval, and reactivation of a cell ensemble triggers the retrieval of the corresponding memory. Moreover, artificial reactivation of a specific neuronal ensemble corresponding to a pre-stored memory can modify the acquisition of a new memory, thereby generating false or synthetic memories. However, these studies employed a combination of sensory input and artificial stimulation of cell ensembles. Until now, researchers had not linked two distinct memories using completely artificial means.
With that goal in mind, Inokuchi and Noriaki Ohkawa of the University of Toyama used a fear-learning paradigm in mice followed by a technique called optogenetics, which involves genetically modifying specific populations of neurons to express light-sensitive proteins that control neuronal excitability, and then delivering blue light through an optic fiber to activate those cells. In the behavioral paradigm, one group of mice spent six minutes in a cylindrical enclosure while another group explored a cube-shaped enclosure, and 30 minutes later, both groups of mice were placed in the cube-shaped enclosure, where a foot shock was immediately delivered. Two days later, mice that were re-exposed to the cube-shaped enclosure spent more time frozen in fear than mice that were placed back in the cylindrical enclosure.
The researchers then used optogenetics to reactivate the unrelated memories of the safe cylinder-shaped environment and the foot shock. Stimulation of neuronal populations in memory-related brain regions called the hippocampus and amygdala, which were activated during the learning phase, caused mice to spend more time frozen in fear when they were later placed back in the cylindrical enclosure, as compared with stimulation of neurons in either the hippocampus or amygdala, or no stimulation at all.
The findings show that synchronous activation of distinct cell ensembles can generate artificial links between unrelated pieces of information stored in memory, resulting in long-lasting changes in behavior. “By modifying this technique, we will next attempt to artificially dissociate memories that are physiologically connected,” Inokuchi says. “This may contribute to the development of new treatments for psychiatric disorders such as post-traumatic stress disorder, whose main symptoms arise from unnecessary associations between unrelated memories.”
More information: Cell Reports, Ohkawa et al.: “Artificial Association of Pre-Stored Information to Generate a Qualitatively New Memory” www.cell.com/cell-reports/abst… 2211-1247(15)00270-3
A group of researchers from Penn State have pushed the realm of possibilities for nanotechnology further as they have successfully steered a nanomotor inside of a human cell. This is the first time this feat has been accomplished. The team of chemists, biologist, and engineers was led by Tom Mallouk and has been published in Angewandte Chemie International Edition.
Nanomotors have been studied in vitro more more than a decade now. The hope is that eventually, they could be used inside of human cells for biomedical research. This nanotechnology could revolutionize drug delivery and even perform surgery in order to increase quality of life in the least invasive way possible. The earliest models were nonfunctional in biological fluid due to their fuel source. A huge breakthrough came later when the nanomotors were able to be powered externally via acoustic waves. The nanomotors used inside the human cells for the latest study were controlled by the ultrasonic waves as well as magnets.
The researchers used HeLa cells, derived from a long-lived line of cervical cancer cells, to study the nanomotors. Getting past the cell membrane was easy, as the cells ingested the nanomotors themselves. Once inside, the ultrasound was turned on and the nanomotors began to spin and move around the cell. If the signal was turned up even higher, the nanomotor can spin like a propeller, chopping up the organelles inside the cell. They were even able to puncture the cell membrane, finishing off the death sentence. Used at low powers, the nanomotor was able to move around the cell without causing any damage.
The addition of magnets gave an important advantage: steering. The motors are also able to be controlled individually, allowing the operator to take a much more targeted approach to killing diseased cells.
Ultimately, the researchers hope that one day the rocket-shaped gold nanorods will be able to move in an out of the cells without causing damage. The individual units could communicate with one another to target disease in the body, maximizing the efficacy of the treatment or even making the correct diagnosis. Working toward the goal of creating such advanced nanotechnology will not only push the boundaries of nanoengineering, but will increase our understanding of chemical and biological processes at the cellular level as well.
“The assembly of a rotating HeLa cell/gold rod aggregate at an acoustic nodal line in the xy plane. The video was taken under 500X overall magnification except for 00:23 – 00:32 and 01:16 – 01:42, where a 200X overall magnification was used.” Credit: Mallouk Lab, Penn State
“Very active gold nanorods internalized inside HeLa cells in an acoustic field. A demonstration of very active gold nanorods internalized inside HeLa cells in an acoustic field. This video was taken under 1000X magnification in the bright field, with most of the incoming light blocked at the aperture.” Credit: Mallouk Lab, Penn State