Date of Degree
PhD (Doctor of Philosophy)
Ryan T. LaLumiere
First Committee Member
John H Freeman
Second Committee Member
Mark S Blumberg
Third Committee Member
Jason J Radley
Fourth Committee Member
Michelle W Voss
Previous research investigating the neural circuitry underlying memory consolidation has primarily focused on single “nodes” in the circuit rather than the neural connections between brain regions, despite the likely importance of these connections in mediating different aspects or forms of memory. This focus has, in part, been due to technical limitations; however the advent of optogenetics has altered our capabilities in this regard, enabling optical control over neural pathways with temporal and spatial precision. The current set of experiments took advantage of optogenetics to control activity in specific pathways connecting brain regions in rats immediately after different kinds of learning.
Chapter 2 first established the use of optogenetics to manipulate activity in the basolateral amygdala (BLA), which has been shown to modulate memory consolidation for a variety of types of learning likely through its connections to various downstream regions. Using a one-trial inhibitory avoidance task, a simple and robust fear learning paradigm, we found that both post-training stimulation and inhibition of BLA activity could enhance or impair later retention of the task, respectively. Enhancement was specific to stimulation using trains of 40, but not 20, Hz light pulses.
Chapters 3 and 4 examined the projections from the BLA to the ventral hippocampus (VH) and medial entorhinal cortex (mEC) as the BLA’s ability to influence the consolidation for many types of memory is believed to be mediated through discrete projections to distinct brain regions. Indeed, the BLA innervates both structures, and prior studies suggest that the mEC and VH have distinct roles in memory processing related to contextual and nociceptive (footshock) learning, such as those involved in contextual fear conditioning (CFC). Optogenetic stimulation or inhibition of the BLA-VH or BLA-mEC pathway after training on a modified CFC task, in which the nociceptive or emotional stimulus (the footshock) and the context are separated, enabled experimental manipulations to selectively affect the consolidation for learning about one component and not the other. Optogenetic stimulation/inhibition was given to each candidate pathway immediately after the relevant training to determine its role in influencing consolidation for that component of the CFC learning. Chapter 3 results showed that stimulation of the BLA-VH pathway following footshock, but not context, training enhanced retention, an effect that was specific to trains of 40 Hz stimulation. Post-footshock photoinhibition of the same pathway impaired retention for the task. Similar investigations of the BLA-mEC pathway in Chapter 4 produced complementary findings. Post-context, but not footshock, stimulation of the pathway enhanced retention. In this particular case, only trains of 8 Hz stimulation were effective at enhancing retention.
These results are the first, to our knowledge, to find that BLA inputs to different structures selectively modulate consolidation for different aspects of learning, thus enhancing our understanding of the neural connections underlying the consolidation of contextual fear conditioning and providing a critical foundation for future research.
Multiple brains regions are known to be involved in emotionally influenced memory consolidation, an area of research of particular importance to brain-based disorders such as posttraumatic stress disorder (PTSD) and phobias, yet we know little about the specific and distinct neural pathways involved in different memory processes. We sought to better understand the neural circuitry underlying the consolidation of different aspects of memory involved in contextual fear conditioning, using a technique called optogenetics that allows activation or inactivation of certain brain regions or pathways via light-sensitive proteins expressed in the brain.
Our results show that posttraining manipulations of a region called the basolateral amygdala (BLA) can lead to both enhancement and impairment when memory is later tested. Importantly, the enhancement is only seen when a certain frequency of stimulation (here, 40 Hz) is used. Investigation of pathways between the BLA and ventral hippocampus suggest this pathway is important for footshock, but not context, learning in a task that requires both kinds of information. Conversely, the pathway between the BLA and medial entorhinal cortex is involved in context, but not footshock, learning.
This research is the first of its kind to examine different pathways from the BLA to determine their roles in the consolidation of different kinds of learning. This approach can be used to look at other pathways involved in learning and memory, but also pathways involved in other functions or disorders.
basolateral amygdala, contextual fear conditioning, medial entorhinal cortex, Memory Consolidation, Optogenetics, ventral hippocampus
x, 99 pages
Includes bibliographical references (pages 82-99).
Copyright © 2016 Mary Louise Huff
Huff, Mary Louise. "Separate basolateral amygdala projections to the hippocampal formation differentially modulate the consolidation of contextual and emotional learning." PhD (Doctor of Philosophy) thesis, University of Iowa, 2016.