title: Aging and learning-specific changes in single-neuron activity in CA1 hippocampus during rabbit trace eyeblink conditioning.
abstract: Rabbit trace eyeblink conditioning is a hippocampus-dependent task in which the auditory conditioned stimulus (CS) is separated from the corneal airpuff unconditioned stimulus (US) by a 500-ms empty trace interval. Young rabbits are able to associate the CS and US and acquire trace eyeblink conditioned responses (CRs); however, a subset of aged rabbits show poor learning on this task. Several studies have shown that CA1-hippocampal activity is altered by aging; however, it is unknown how aging affects the interaction of CA1 single neurons within local ensembles during learning. The present study examined the extracellular activity of CA1 pyramidal neurons within local ensembles in aged (29-34 mo) and young (3-6 mo) rabbits during 10 daily sessions (80 trials/session) of trace eyeblink conditioning. A single surgically implanted nonmovable stereotrode was used to record ensembles ranging in size from 2 to 12 separated single neurons. A total of six young and four aged rabbits acquired significant levels of CRs, whereas five aged rabbits showed very few CRs similar to a group of five young pseudoconditioned rabbits. Pyramidal cells (2,159 total) were recorded from these four groups during training. Increases in CA1 pyramidal cell firing to the CS and US were diminished in the aged nonlearners. Local ensembles from all groups contained heterogeneous types of pyramidal cell responses. Some cells showed increases while others showed decreases in firing during the trace eyeblink trial. Hierarchical clustering was used to isolate seven different classes of single-neuron responses that showed unique firing patterns during the trace conditioning trial. The proportion of cells in each group was similar for six of seven response classes. Unlike the excitatory modeling patterns reported in previous studies, three of seven response types (67% of recorded cells) exhibited some type of inhibitory decrease to the CS, US, or both. The single-neuron response classes showed different patterns of learning-related activity across training. Several of the single-neuron types from the aged nonlearners showed unique alterations in response magnitude to the CS and US. Cross-correlation analyses suggest that specific single-neuron types provide more correlated single-neuron activity to the ensemble processing of information. However, aged nonlearners showed a significantly lower level of coincident pyramidal cell firing for all cell types within local ensembles in CA1.
authors.affiliation: Department of Cell and Molecular Biology and Institute for Neuroscience, Northwestern University Medical School, Chicago, Illinois 60611, USA.
authors.forename: M D
authors.initials: MD
authors.lastname: McEchron
authors.forename: A P
authors.initials: AP
authors.lastname: Weible
authors.forename: J F
authors.initials: JF
authors.lastname: Disterhoft
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001767:Blinking / Q000502:physiology*; D003215:Conditioning, Eyelid / Q000502:physiology; D004566:Electrodes; D004594:Electrophysiology; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology*; D011817:Rabbits