A pinboard by
Mary Huff

Postdoctoral Research Associate, Stowers Institute


Loss of memory is the earliest and most common symptom of many diseases of the nervous system. Despite intense efforts, it remains unclear how and why memory is lost - can we no longer form a memory? Or can we not hold the memory? Or have we lost the ability to recall? To understand loss of memory, therefore we first need to understand how normal memory is acquired, stored and recalled and thus is the first line of our research. We are targeting key molecular mechanisms at multiple levels of memory processing to better define what mechanisms are important at different stages of normal learning. Recent technical advances in light-sensitive proteins allow us to selectively inactivate these target proteins in a mouse model in a temporally and spatially restricted manner. Moreover, previous work from our lab has discovered that there are proteins in the nervous system that normally form amyloids and are required for memory to persist unlike the amyloids commonly discussed in disease. This suggested that amyloid diseases may be due to loss of normal function of amyloids, a completely novel way of looking at the cause of memory loss in Alzheimer’s and other disease states. Therefore, we want understand the synaptic events that help store a memory stably again using light-activated tagging of proteins that are being activated during the various phases of memory formation, storage, and recall. Understanding these mechanisms during normal learning will inform what goes wrong in the disease state.


Posttraining optogenetic manipulations of basolateral amygdala activity modulate consolidation of inhibitory avoidance memory in rats.

Abstract: Memory consolidation studies, including those examining the role of the basolateral amygdala (BLA), have traditionally used techniques limited in their temporal and spatial precision. The development of optogenetics provides increased precision in the control of neuronal activity that can be used to address the temporal nature of the modulation of memory consolidation. The present experiments, therefore, investigated whether optogenetically stimulating and inhibiting BLA activity immediately after training on an inhibitory avoidance task enhances and impairs retention, respectively. The BLA of male Sprague-Dawley rats was transduced to express either ChR2(E123A) or archaerhodopsin-3 from the Halorubrum sodomense strain TP009 (ArchT). Immediately after inhibitory avoidance training, rats received optical stimulation or inhibition of the BLA, and 2 d later, rats' retention was tested. Stimulation of ChR2(E123A)-expressing neurons in the BLA using trains of 40-Hz light pulses enhanced retention, consistent with recording studies suggesting the importance of BLA activity at this frequency. Light pulses alone given to control rats had no effect on retention. Inhibition of ArchT-expressing neurons in the BLA for 15 min, but not 1 min, significantly impaired retention. Again, illumination alone given to control rats had no effect on retention, and BLA inhibition 3 h after training had no effect. These findings provide critical evidence of the importance of specific frequency patterns of activity in the BLA during consolidation and indicate that optogenetic manipulations can be used to alter activity after a learning event to investigate the processes underlying memory consolidation.

Pub.: 13 Feb '13, Pinned: 30 Jun '17