1. Zicong Zhang 2011.08.15

2. Authors Wendy A. Suzuki Professor of Neural Science and Psychology, New York University Research interest: Organization of memory in the medial temporal lobe and the effects of exercise on learning, memory and cognition. Yuji Naya Post-Doc fellow, associate faculty member in Suzuki’s Lab. He is best known for the groundbreaking work he did in collaboration with Yasushi Miyashita on the representation of well-learned associations within the perirhinal cortex. 2

3. Backgrounds The human medial temporal lobe (MTL) is critical for episodic memory presumably because of its role in binding individual stimuli or events to their temporal and spatial contexts. Computation models: Cortical association areas signal information about items; Parahippocampal regions signal information about items along with their temporal context; Hippocampus (HPC) supervises these item- context associations. 3

4. Backgrounds fMRI studies in humans report both HPC and parahippocampal activation during tasks of temporal-order memory. Recent neurophysiological studies in the rodent have highlighted the role of HPC in signaling either a particular time within a trial or incremental timing across the entire recording session. 4

5. Questions and Ideas Little is known about the neurophysiological basis of how item and timing information is integrated within MTL. In this study, neural activities from MTL areas and a control visual area were recorded as nonhuman primates performed a temporal- order memory task that required encoding of two visual items and their temporal order. 5

6. Training Design “Time cells”: neurons whose responses differentiated between the cue 1 and cue 2 periods, signaling relative timing between cue presentations or temporal order of cue presentations. “Item cells”: neurons that showed significant stimulus-selective activity during either cue 1 or cue 2. Cue 1 delay period 6

7. Recordings “Time cells”: neurons whose responses differentiated between the cue 1 and cue 2 periods, signaling relative timing between cue presentations or temporal order of cue presentations. “Item cells”: neurons that showed significant stimulus- selective activity during either cue 1 or cue 2. 7

8. Recordings Two-dimensional plots of the population average LFP spectrogram in all areas. The gamma band activity (>30 Hz) in HPC increased during the cue 1 delay period and was significantly stronger during cue 2 than cue 1. 8

9. Question 2 How did the population of cells signal time information? 9

10. Population Vector Analysis: backgrounds Original Idea: to explain how populations of motor cortex neurons encode movement direction. Basis: individual neurons tended to discharge more for movements in particular directions, the so-called preferred directions for individual neurons. In the population vector model, individual neurons 'vote' for their preferred directions using their firing rate. The final vote is calculated by vectorial summation of individual preferred directions weighted by neuronal rates. “Population vectors were used to examine information represented by a population of prefrontal activity and its temporal change during spatial working memory processes…” (Takeda and Funahashi, 2004) In the present study: “to characterize the temporal dynamics of time cells observed throughout the MTL.” 10

11. Population Vector Analysis for time cells Normalized distances (NDs) from the cue 1 states (solid circles) and the cue 2 states (open squares) in each area. Population vectors were constructed from the responses of all individual time cells for 40-ms time bins throughout the cue 1 delay period. Their temporal dynamics were characterized relative to two “template” time periods defined as the cue 1 and the cue 2 states. HPC: the distance from the two templates changed constantly. ERC: only the one from cue 1 state gradually increase. PRC: sudden shifted at the early period and remained relatively constant. 11

12. “To determine which area provided the most accurate representation of the cue 2 state before the presentation of cue 2, we asked which of the three areas exhibited the shortest distance to the cue 2 state during the last quarter (240 ms) of the cue 1 delay period.” Population Vector Analysis for time cells 12

13. Summary 1 As a population, HPC time cells provide an incremental timing signal that gives an estimate of the relative time from the last cue presentation as well as an estimate of the relative time to the next cue presentation. 13

14. Question 3 How did the MTL represent item information? 14

15. Item information represented in MTL “PRC and TE represented the same items across the two cue periods. A time effect was revealed in PRC such that the response to the neuron’s preferred stimulus differed across cue 1 and cue 2.” Distributions of correlation coefficients between cue 1 and cue 2. Mean discharge rates and SEM during cue 1 and cue 2. “The small correlation coefficients in ERC can be explained by the lack of stimulus selectivity in one of the two cue periods. This differential level of stimulus selectivity between cue periods can serve to integrate item information with a relative timing signal.” 15

16. Question 4 Whether the PRC item cells integrate item and temporal order information by modulating their stimulus-selective response properties across the cue periods? 16

17. Differential time effect in PRC C: Normalized vector distances between cue 1 and cue 2 D: Normalized mean discharge rates E: Kurtosis measure Suggesting “a more prominent time effect in PRC” The differential time effect was not due to general changes in firing rates Suggesting that “PRC differentiates between the cue 1 and cue 2 periods by changing the sharpness of its stimulus- selective response” 17

18. Hypothesized information flow across MTL regions and TE. HPC provides a robust incremental timing signal that may serve to anchor the timing to events within an episode. ERC neurons can signal incremental timing information as well as integrate item and time information at a lower amplitude. PRC neurons integrate time and item information by modulating their stimulus- selective response properties across temporally distinct stimulus presentations. Hypothesis: the incremental timing signal in HPC is conveyed to PRC via ERC, where it is integrated with item information from TE and converted into a discrete item-based temporal order signal. 18

19. References Takeda, K. and S. Funahashi, Population vector analysis of primate prefrontal activity during spatial working memory. Cereb Cortex, 2004. 14(12): p. 1328-39 “Neural ensemble”. From Wikipedia. 19