The long-term goal is to understand how the brain remembers. Memory's ultimate purpose is informed action. We recall the past to anticipate potential outcomes of familiar situations. Episodic memory requires the hippocampus and is devastated by Alzheimer's disease, yet precisely how hippocampal neurons inform such memory is unknown.
The aim now is to identify patterns of hippocampal neuronal activity required for memory. As rats performed a hippocampus-dependent """"""""episodic-like"""""""" memory task, the firing patterns of hippocampal neurons varied with imminent or recent events when other aspects of behavior were identical, revealing prospective or retrospective coding, respectively.
Three Aims will systematically manipulate hippocampus-dependent memory demand qualitatively and quantitatively:
Aim 1 will test if prospective and retrospective activities predict hippocampus-dependent spatial memory performance while error rate is varied systematically via interference. Retrospective and especially prospective activity should predict changes in ongoing memory performance.
Aim 2 will test the generality of the results in Aim 1 by assessing neuronal activity in two non-spatial cue discrimination tasks that differ in hippocampus dependence. Rats will perform the same behaviors as in Aim 1: one task is unaffected by hippocampal lesions, the other should be impaired. Memory demand and error rates will be varied by altering the delay and pattern of stimulus presentation. If the active recruitment of memory coding by hippocampal neurons requires specific memory demands, then memory coding should increase as those demands increase and decline with errors; without those demands, such activity should be minimal and unrelated to errors.
Aim 3 will assess coding during performance of a novel non-spatial task that requires the hippocampus and flexible memory retrieval, but not recent memory. Rats trained to approach different non-spatial goal objects depending on their deprivation state (hunger or thirst) were impaired after hippocampal lesions. If prospective coding reflects a general computational process by which the hippocampus signals impending events independent of recent memory, then neuronal activity should anticipate choice selection and predict errors.
Each aim will assess population and temporal coding and their interaction. The research should inform the design of rational treatments for amnesia (e.g. by stroke or Alzheimer's disease), including the future development of neural prostheses. ? ?
|Guise, Kevin G; Shapiro, Matthew L (2017) Medial Prefrontal Cortex Reduces Memory Interference by Modifying Hippocampal Encoding. Neuron 94:183-192.e8|
|Harony-Nicolas, Hala; Kay, Maya; Hoffmann, Johann du et al. (2017) Oxytocin improves behavioral and electrophysiological deficits in a novel Shank3-deficient rat. Elife 6:|
|Riceberg, Justin S; Shapiro, Matthew L (2017) Orbitofrontal Cortex Signals Expected Outcomes with Predictive Codes When Stable Contingencies Promote the Integration of Reward History. J Neurosci 37:2010-2021|
|Seip-Cammack, Katharine M; Young, James J; Young, Megan E et al. (2017) Partial lesion of the nigrostriatal dopamine pathway in rats impairs egocentric learning but not spatial learning or behavioral flexibility. Behav Neurosci 131:135-42|
|Golden, Sam A; Heshmati, Mitra; Flanigan, Meghan et al. (2016) Basal forebrain projections to the lateral habenula modulate aggression reward. Nature 534:688-92|
|Shapiro, Matthew (2015) A limited positioning system for memory. Hippocampus 25:690-6|
|Christoffel, Daniel J; Golden, Sam A; Walsh, Jessica J et al. (2015) Excitatory transmission at thalamo-striatal synapses mediates susceptibility to social stress. Nat Neurosci 18:962-4|
|Tavares, Rita Morais; Mendelsohn, Avi; Grossman, Yael et al. (2015) A Map for Social Navigation in the Human Brain. Neuron 87:231-43|
|Fletcher, Bonnie R; Hill, Gordon S; Long, Jeffrey M et al. (2014) A fine balance: Regulation of hippocampal Arc/Arg3.1 transcription, translation and degradation in a rat model of normal cognitive aging. Neurobiol Learn Mem 115:58-67|
|Seip-Cammack, Katharine M; Shapiro, Matthew L (2014) Behavioral flexibility and response selection are impaired after limited exposure to oxycodone. Learn Mem 21:686-95|
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