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Jian-Zhong Xiang, Malcolm W Brown  Neuron 

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1 Neuronal Responses Related to Long-Term Recognition Memory Processes in Prefrontal Cortex 
Jian-Zhong Xiang, Malcolm W Brown  Neuron  Volume 42, Issue 5, Pages (June 2004) DOI: /j.neuron

2 Figure 1 Task Details (A) Example task sequences. The serial recognition task used pictures of naturalistic scenes or objects. Each letter represents a particular picture; the uppercase letters are novel stimuli, and the lowercase letters are familiar stimuli. The conditional discrimination task used triplets of geometric shapes. The triangle was red, the square was black, the central shape was green with a black dot, and the background was yellow. For each of the four types of trial containing a specific triplet, no one shape in isolation could be used to solve the task. “L” and “R,” the correct responses are touches to the left or right side of the screen. (B) Intratrial timing. Each trial starts with a cue light (“C”), followed by a stimulus (“S”). Within time period “T,” the animal must make a behavioral response (touch the correct side of the screen) to get a reward (“R”). The trial finishes with a variable (1–3 s) intertrial interval (dashed lines). Neuron  , DOI: ( /j.neuron )

3 Figure 2 Recording Sites
(A) Recordings were made 1–15 mm anterior (“A”) to the sphenoid bone, which is approximately 20 mm anterior to the intraaural line, as shown on the lateral view (left). The regions in which recordings were made, i.e., anterior cingulate gyrus (ACG) and orbital (PFCo), ventromedial (PFCvm), and dorsolateral (PFCdl) prefrontal cortex, are shown (right) outlined at “5A” level. (B) Regional distribution of the visually differential neurons. These have been plotted onto outline frontal sections at the given distances (in mm) in front of the sphenoid bone (Xiang and Brown, 1998). Neuron  , DOI: ( /j.neuron )

4 Figure 3 Responses of Excitatory Visually Differential Neurons Simultaneously Recorded in Orbital Prefrontal Cortex (A) The different response patterns of the neurons are illustrated for the same trials containing first (“1”) or second (“2”) presentations of novel (“N”) or familiar (“F”) stimuli. The action potential waveforms of the neurons are inserted in the first column. Note the different action potential shapes; the amplitudes also differed but have been rescaled. Peristimulus time histograms (bin width, 100 ms) are shown above rasters (ten individual stimuli). Trials of the same type of stimuli were originally separated by intervening trials of other types of stimuli but have been sorted and pooled together by offline computation. The recency neuron signals that a stimulus has been seen recently; its responses to N1 and F1 were significantly (p < 0.001) smaller than its responses to N2 and F2. The familiarity neuron signals that a stimulus is familiar rather than novel but not that it has been seen recently; its responses to N1 and N2 were significantly smaller (p < 0.001) than its responses to F1 and F2. The novelty neuron is selectively responsive to first presentations of novel stimuli; its responses to N1 were significantly smaller (p < 0.001) than its responses to N2, F1, or F2. (B) The cumulative action potential counts after stimulus onset are given for the novel and familiar trials for the familiarity neuron shown in (A). The visual latency is ∼120 ms, and the differential latency is ∼260 ms. Thus, this neuron's responses differed significantly between novel and familiar trials by ∼260 ms. (C) In contrast, there were no significant differences in mean eye position or its variance between the types of trials in the 500 ms following stimulus onset. Thus, the differences in neuronal activity cannot readily be explained as being due to differences in eye position. Neuron  , DOI: ( /j.neuron )

5 Figure 4 Inhibitory Responses of a Familiarity Neuron in the Ventromedial Prefrontal Cortex The neuronal responses to first and second presentations of novel (left) and familiar (right) stimuli are shown as peristimulus time histograms (bin width, 100 ms) above rasters. Note that the inhibitory responses to the novel stimuli were significantly (p < 0.001) smaller than those to the familiar stimuli. The latency of the visual response was ∼130 ms, and the differential latency was ∼245 ms. Neuron  , DOI: ( /j.neuron )

6 Figure 5 Differential Latencies for the Populations of Excitatory Incremental Visually Differential Neurons in the Prefrontal Cortex (Left) Plotted are the cumulated counts (30 ms bins) of action potentials from stimulus onset (time zero) for the different types of trial averaged across each of the different types of neurons in the three areas. Comparisons were made for the response of each neuron in each area between the first and second presentations for the recency neurons; between the novel and familiar presentations for the familiarity neurons; and between the first and second presentations of novel stimuli and between the first presentations of novel and familiar stimuli for novelty neurons. To determine the differential latency for each type of response, the mean bin counts for the different types of trial for each of the differential neurons of the particular type in each of the areas were subjected to an ANOVA with repeated measures. There was no significant interaction between the factors area, time, and type of trial except for recency neurons [F(34, 1872) = 1.50; p = 0.03]. For each of the four types of response, there was a highly significant (p < 0.001) interaction between time (bin number) and the type of trial. The mean time of the earliest bin for which the difference between the types of trials was significant (Student's t test; p < 0.05) was taken as the mean latency for a given population of neurons. In every case, all subsequent bins were also significant. (Table to right) The mean differential latencies (midpoints of 30 ms bin) of different types of visually differential neurons in the recorded areas. Neuron  , DOI: ( /j.neuron )

7 Figure 6 Memory Spans (A) Mean responses across different intervals for the three types of excitatory incremental differential neurons in the three different areas. The sample comprised all the D neurons with excitatory incremental responses for which there were data at all intervals. *Indicates a significant difference between mean responses to the first (“C”) and subsequent presentations within an area and type of neuron (paired Student's t tests). The significance of differences from the initial mean response was determined for the successively greater intervals using a level of p = 0.05 as long as the difference for each successive interval was significant. When a difference failed to reach significance for a given interval, the next interval's difference was tested after correction for multiple tests (i.e., using p = after one failure to reach significance, p = after two, and so on). Note that to compare the responses at 24 hr with those to the first presentations of the same stimuli, the same trial files were shown to the animals after a 24 hr delay. (B) Memory spans of 24 hr. Displayed are population mean responses for excitatory incremental visually differential neurons with a memory span lasting ∼24 hr in prefrontal cortex. Illustrated are neurons which had mean responses that were significantly larger when stimuli were repeated after an ∼24 hr delay than when they were first presented. For these selected samples, mean responses at all time intervals were significantly larger for the subsequent presentations than for the first presentations of the stimuli for recency, familiarity, and novelty neurons pooled across the areas. (C) Percentages of all D neurons that had 24 hr memory spans for the different types in the different areas. Neuron  , DOI: ( /j.neuron )


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