Neurons and networks organizing and sequencing memories

Abstract

Hippocampal CA1 and CA3 neurons sampled randomly in large numbers in primate brain show conclusive examples of hierarchical encoding of task specific information. Hierarchical encoding allows multi-task utilization of the same hippocampal neural networks via distributed firing between neurons that respond to subsets, attributes or "categories" of stimulus features which can be applied in events in different contexts. In addition, such networks are uniquely adaptable to neural systems unrestricted by rigid synaptic architecture (i.e. columns, layers or "patches") which physically limits the number of possible task-specific interactions between neurons. Also hierarchical encoding is not random; it requires multiple exposures to the same types of relevant events to elevate synaptic connectivity between neurons for different stimulus features that occur in different task-dependent contexts. The large number of cells within associated hierarchical circuits in structures such as hippocampus provides efficient processing of information relevant to common memory-dependent behavioral decisions within different contextual circumstances. This article is part of a Special Issue entitled SI: Brain and Memory.

Keywords: Hierarchical encoding; Hippocampal neurons; Memory; Nonhuman primates; Nonlinear hierarchical model; Retention and retrieval.

Figure 1. Dual Trial-Delayed Match to Sample Memory Task

A. The Rule-based DMS task: NHPs are seated in a primate chair with a shelf-counter in front of them facing a large display screen. During task performance the right hand position on the counter top is tracked by a small LCD camera positioned 30 cm above the hand and displayed as a bright yellow cursor on the projection screen. The screen displayed 2-8 clipart images (# of images) per trial which were placed randomly across each of the 8 possible screen positions (Target positions). Representative screen displays and screen images are shown for successive Phases of the DMS task: Start-Rule, Sample, Delay and Match, in which two types of trials are possible. The display of the Match phase on the right (Match) shows correct selections for both types of trial indicated by the Start-Rule image (left) as either: 1)a Spatial trial in which the correct response (blue arrow) was placement of the cursor into the same spatial location on the screen in which the Sample image was displayed and responded to in the Sample phase, irrespective of image features, or; 2) an Object trial in which the same image shown in the Sample phase was selected (red arrow) irrespective of which location on the screen it occupied. The Delay interval between the occurrence of the Sample response and presentation of the Match phase was of variable duration (5.0-90.0s) on each trial. B&C. Average behavioral performance (% correct) and Match response latencies of trained animals (n=6) on each type of trial, shown as a function of the number of distracter images presented in the Match phase. D. List of abbreviated labels for task-related attributes of images presented in Sample phase recorded consistently from hippocampal cells during either Spatial or Object trials for at least 60 daily sessions consisting of 100 trials. Abbreviated labels denote Simple cell features in the hierarchical encoding arrays shown in Figures 2-4.

Figure 2. Hierarchical Encoding of Spatial and Object Trials

A: Diagram depicts hierarchical encoding of hippocampal cells recorded on Spatial (blue) and Object (red) trials as time transitions from the Sample (lower 2 levels) to Match (upper two levels) phase of the DMS task. Labels of Simple cells in the lower two rows show designation of trial type from the prior Start Rule response (spatial-Sp and object-Ob), and for the different attributes of images presented in the Sample phase of the task as listed in Figure 1D. Arrows (blue and red) indicate associated synaptic connections with Conjunctive cells in the Sample phase (sL, sT; sC, sH) that transfer firing to the Match phase (L,T,C, H) and project to higher category TT cells (mLT and mHC). TT cells then project to appropriate Match Response cells (rLT, rHC) for selection of either the appropriate image (Object trial hierarchy), or location on the screen (Spatial trial hierarchy), corresponding to the Sample phase response. B: Average firing rate profiles are shown for two Conjunctive cells (sH and sL) in the above hierarchy for both phases of the task (Sample and Match) during each type of DMS trial (Spatial and Object).

Figure 3. Multiple Hierarchical Array Encoding

Hierarchical representation within the same hippocampal cell population of trial-specific images on 4 different trials. A. This illustrates the high degree of overlap and cross-connectivity that is possible within the same homogeneous cell population in which connectivity with Conjunctive cells is controlled by categorized Simple cell image encoding in the Match phase. B. Shared hierarchical of encoding by the same Simple hippocampal cells that encode events on more than one type of trial due to the occurrence of similar features in images presented on other trials. The green and blue labeled hierarchies involve the same Simple and Conjunctive hippocampal cells shown in Fig 3A, however the red and purple hierarchies employ some of those same Simple and Conjunctive cells (L and sh) to encode different spatial (B) or image (C) features on a different trials as shown by the dotted connections to separate TT cells in the Match phase (mLB & mCsh).

Figure 4. Extraction of Hierarchical Spatiotemporal Codes via Nonlinear MIMO Model

A. Depiction of spatiotemporal firing patterns extracted by a multi-input multi-output (MIMO) nonlinear model (Berger et al., 2011) applied to simultaneously recorded cells (Chs. 01-04) in CA3 (top) and CA1 (bottom) with two separate multi-array probes. B. MIMO model extracted firing patterns of multiple cells (n=8) displayed in a “heat map” style to emphasize spatiotemporal patterns recorded at the time of Sample phase image presentation (SP) and response (SR) on both correct and error, Spatial vs. Object trials. Intensity of firing is scaled across cells from low (4 Hz, green) to high (10 Hz, red) rates during Sample presentation (SP) and response (SR) depicted by the blue and red arrows in A. Spatiotemporal heat map firing patterns differ as a function of the type of trial as well as whether the trial was responded to correctly (Correct code) or incorrectly (“Wrong” code). C. Extraction of hierarchical spatiotemporal firing in this manner provides insight into why some trials may not be responded to correctly. “Wrong” code trial firing patterns are less intense but on some occasions also reflect suppressed hierarchical processing of the opposite trial type (i.e. Object trial) as shown in the heat maps in B and the hierarchical diagrams in C (“Wrong” code). Since retention of the Start-Rule code indicating the ‘type of trial’ is also critical for effective performance in the Match phase (C: Correct Trial Sp response), errors may also indicate encoding by the wrong Start-Rule Simple cells in the Sample phase of the task (C: ‘Wrong Trial’ object response).

Figure 5. Memory Encoding in Hippocampus

An important issue with respect to the functional significance of hierarchical encoding is whether processing eventually conforms to the overall input-output processing features of the structure involved. This is required otherwise the processed information does not get transmitted to the appropriate effector (i.e. behavioral response) system. The average peak firing rates of cells involved in hierarchical processing in CA3 and CA1 were compared and showed similar firing tendencies in the critical phases of both types of trial, as well as on error trials in which the output structure CA1 showed the same decrease as in CA3 across all task phases. Although there are other reasons why such correspondence in average firing may not occur, such as initiation of the “wrong” code as shown in Figure 4B, the substrates required for successful performance are not possible without ‘consistent utilization’ of the appropriate Conjunctive and TT cells in the CA1output region of hippocampus.