Learning, Memory and Plasticity in the Rodent Brain
mCherry expression in hippocampal area CA1 reflecting localized expression of ChannelRhodopsin
Research Overview
The ability to use experience to guide behavior (to learn) is one of the most remarkable abilities of the brain. Our goal is to understand how activity and plasticity in neural circuits underlie both learning and the ability to use learned information to make decisions. In particular, our laboratory focuses on the circuitry of the hippocampus and anatomically related regions. We use a combination of techniques, including large scale multielectrode recording, targeted optogenetic interventions and behavioral manipulations of awake, behaving animals to understand how the brain learns and remembers.Anatomical organization of the hippocampus
The hippocampal
formation has a unique anatomical organization in that the connectivity
between adjacent hippocampal regions is almost exclusively
unidirectional. The majority of neocortical input to the hippocampus
comes in through the superficial layers of the entorhinal cortex and
connections proceed through the dentate gyrus, to CA3 and on to CA1
(the hippocampus proper), and then to the subiculum. Nearly all
neocortically bound outputs from the hippocampus originate in CA1 and
the subiculum and target cells in the deep layers of the entorhinal
cortex, which projects both to numerous neocortical regions as well as
to back to the superficial layers of the entorhinal cortex. Our
research uses that organization to compare patterns of activity across
regions and to use the similarities and differences among the patterns
to identify the transformations that occur in the hippocampal circuit.
An animal model for hippocampal function
Numerous
researchers have shown that a human without a hippocampus is unable to
form new memories of facts or events. In rodents these same structures
play an essential role in animal's abilities to learn about and
remember complex associations, including tasks where the animal must
learn and remember information about a set of spatial cues in order to
navigate through an environment. Event/fact memory in humans and
spatial memory in rodents both require learning complex relationships,
and that parallel strongly suggests that qualitatively similar
processing occurs in the human and the rat hippocampus.
Learning in the hippocampus and cortex
Previous studies
have shown that neurons throughout the hippocampal formation show place
specific firing patterns, where a given neuron is active only in a
subregion of the animal's environment. Most of these studies focused on
describing patterns of activity during well learned tasks, and we
therefore know little about neural processing during learning. We have
developed a spatial alternation task that animals can learn over the
course of a few days of exposure. We have shown that rapid learning in
this task requires an intact hippocampus, and thus this task provides a
powerful paradigm for examining the relationship between dynamic
patterns of neural activity and changes in behavior.
Although the hippocampus is essential for spatial learning, storing and retrieving new information requires complex networks spread throughout the brain. One prominent hypothesis states that learning takes place first in the hippocampus and over time information is transferred to neocortical regions in a process known as consolidation. We are therefore recording both in the hippocampus and in downstream areas to understand how hippocampal and cortical circuits could support learning, consolidation and memory guided behavior.
These studies continue to provide important new insights into how the brain changes as animals learn and how memory retrieval might occur, but these insights are fundamentally correlational in nature. We have therefore been developing and apply new techniques, including optogenetic manipulations, to take these correlational hypothesis and turn them into causal understanding. We can now express optically activated channels in specific subpopulations of neurons in the rat hippocampus and activate these channels with an implanted fiber optic. We have also combined this optical activation with large scale multielectrode recording, allowing us to manipulate the circuit and record the results both locally and in more distant brain regions.
Although the hippocampus is essential for spatial learning, storing and retrieving new information requires complex networks spread throughout the brain. One prominent hypothesis states that learning takes place first in the hippocampus and over time information is transferred to neocortical regions in a process known as consolidation. We are therefore recording both in the hippocampus and in downstream areas to understand how hippocampal and cortical circuits could support learning, consolidation and memory guided behavior.
These studies continue to provide important new insights into how the brain changes as animals learn and how memory retrieval might occur, but these insights are fundamentally correlational in nature. We have therefore been developing and apply new techniques, including optogenetic manipulations, to take these correlational hypothesis and turn them into causal understanding. We can now express optically activated channels in specific subpopulations of neurons in the rat hippocampus and activate these channels with an implanted fiber optic. We have also combined this optical activation with large scale multielectrode recording, allowing us to manipulate the circuit and record the results both locally and in more distant brain regions.