Linking hippocampal multiplexed tuning, Hebbian plasticity and navigation.

Three major pillars of hippocampal function are spatial navigation1, Hebbian synaptic plasticity2 and spatial selectivity3. The hippocampus is also implicated in episodic memory4, but the precise link between these four functions is missing. Here we report the multiplexed selectivity of dorsal CA1 neurons while rats performed a virtual navigation task using only distal visual cues5, similar to the standard water maze test of spatial memory1. Neural responses primarily encoded path distance from the start point and the head angle of rats, with a weak allocentric spatial component similar to that in primates but substantially weaker than in rodents in the real world. Often, the same cells multiplexed and encoded path distance, angle and allocentric position in a sequence, thus encoding a journey-specific episode. The strength of neural activity and tuning strongly correlated with performance, with a temporal relationship indicating neural responses influencing behaviour and vice versa. Consistent with computational models of associative and causal Hebbian learning6,7, neural responses showed increasing clustering8 and became better predictors of behaviourally relevant variables, with the average neurometric curves exceeding and converging to psychometric curves. Thus, hippocampal neurons multiplex and exhibit highly plastic, task- and experience-dependent tuning to path-centric and allocentric variables to form episodic sequences supporting navigation

Multisensory control of multimodal behavior: do the legs know what the tongue is doing?

Understanding of adaptive behavior requires the precisely controlled presentation of multisensory stimuli combined with simultaneous measurement of multiple behavioral modalities. Hence, we developed a virtual reality apparatus that allows for simultaneous measurement of reward checking, a commonly used measure in associative learning paradigms, and navigational behavior, along with precisely controlled presentation of visual, auditory and reward stimuli. Rats performed a virtual spatial navigation task analogous to the Morris maze where only distal visual or auditory cues provided spatial information. Spatial navigation and reward checking maps showed experience-dependent learning and were in register for distal visual cues. However, they showed a dissociation, whereby distal auditory cues failed to support spatial navigation but did support spatially localized reward checking. These findings indicate that rats can navigate in virtual space with only distal visual cues, without significant vestibular or other sensory inputs. Furthermore, they reveal the simultaneous dissociation between two reward-driven behaviors

Multisensory Control of Multimodal Behavior: Do the Legs Know What the Tongue Is Doing?

<div><p>Understanding of adaptive behavior requires the precisely controlled presentation of multisensory stimuli combined with simultaneous measurement of multiple behavioral modalities. Hence, we developed a virtual reality apparatus that allows for simultaneous measurement of reward checking, a commonly used measure in associative learning paradigms, and navigational behavior, along with precisely controlled presentation of visual, auditory and reward stimuli. Rats performed a virtual spatial navigation task analogous to the Morris maze where only distal visual or auditory cues provided spatial information. Spatial navigation and reward checking maps showed experience-dependent learning and were in register for distal visual cues. However, they showed a dissociation, whereby distal auditory cues failed to support spatial navigation but did support spatially localized reward checking. These findings indicate that rats can navigate in virtual space with only distal visual cues, without significant vestibular or other sensory inputs. Furthermore, they reveal the simultaneous dissociation between two reward-driven behaviors.</p></div

Navigational performance in the virtual audiovisual spatial navigation task.

<p>(A) Schematic of the virtual environment indicating distal auditory and visual cues and a hidden reward zone and the four start locations. (B) Example paths from a single rat from the 1^st session. The color of each path indicates start location, color coded from the arrows in A. (C) Example paths from the same rat from the 6^th session. (D) Acquisition curve of latency to reward across sessions. F(5,35)  = 4.266, p = 0.0061, Session 1 vs. Session 3: p<0.05, N =  6. (E) Acquisition curve of the distance traveled to reward across sessions. F(5,35)  = 3.00, p = 0.0296, Session 1 vs. Session 5: p<0.05. (F) 2-D histogram of mean occupancy averaged across final four task sessions of asymptotic performance with the smaller reward zone. (G) Example of a probe trial path. (H) Percentage quadrant measures for occupancy time during the final four task sessions performance and during the probe trial. Effect of quadrant: F(3,23)  = 10.15, p = 0.007, F(3,23)  = 10.9, p = 0.0005, respectively.</p

Analysis of reward checking behavior during the virtual audiovisual spatial navigation task.

<p>(A) Acquisition curve of normalized check distance across sessions and during final task performance. This is calculated as: Mean actual distance/Mean randomized distance x 100. Note that the 6^th day of acquisition was lost to malfunction of capacitive sensor. “Final” indicates performance average across the final four task sessions. Effect of session: F(5,35)  = 3.384, p = 0.018, p<0.05 for 1^st vs. 5^th session, N = 6. (B) Normalized check rate across sessions. Effect of session: F(5,35)  = 4.452, p = 0.0049, p<0.05 for 1^st vs. 4^th session (C) 2-D histogram of the normalized check rate averaged across rats during final task performance. (D) Check rate modulation as a function of radial distance away from the reward zone in 4 cm radial bins for final task performance. Effect of bin, F(14,89 = 9.241, p<0.0001, p<0.05 for closest bin relative to 3rd through 15th bins. (E) 2-D p-value map of a single rat’s performance during the final task performance. Red indicates regions where checking behavior was significantly modulated above chance (p<0.01) and blue indicates regions where checking behavior was significantly below chance. (F) Example of actual checking behavior (black line) as a function of radial distance from the reward zone relative to random checking behavior (green line, with shaded SE). Red dots represent points significantly above chance and blue dots represent points significantly below chance.</p

Multisensory contribution to virtual spatial navigation and reward checking.

<p>(A) Schematic of the Audiovisual (AV), Visual (V) only and Auditory (A) virtual spatial mazes. Symbols as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0080465#pone-0080465-g001" target="_blank">Figure 1</a>. (B) Example paths for the three trial types from a single rat. The color of each path indicates start location, color coded from the arrows in A. (C) Median latency and distance to reward for each trial type. Effect of trial type, F(2,17)  = 7.555, p = 0.01, F(2,17)  = 8.911, p = 0.006, respectively. A vs. AV and V: p<0.05 for both measures, N = 6. (D) Percentage occupancy in the target quadrant for the three trial types. Effect of trial type: F(2,17)  = 13.19, p = 0.0064. A vs. AV: p = 0.013, A and V: p = 0.018.</p

Navigational performance and reward checking during the auditory and visual virtual spatial navigation tasks.

<p>(A) Schematic of the auditory task and the visual task. Symbols as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0080465#pone-0080465-g003" target="_blank">Figure 3</a>. (B) Example paths from each task. (C) 2-D histogram of occupancy averaged across rats over 4 sessions for each trial type. (D) 2-D histogram of the normalized check rate averaged across rats over these sessions. White areas indicate insufficient coverage. (E) Percentage of occupancy and check rate in the target quadrant for the two tasks. Two way ANOVA for effect target vs. other quadrants and auditory vs. visual trial types: Effect of quadrant F(1,8)  = 95.16, p< 0.001, Effect of task type: F(1,8)  = 2.08, p<0.001, Interaction of quadrant and task type: F(1,8)  = 2.08, p = 0.002; Effect of quadrant for auditory task: p = 0.097, target quadrant percentage occupancy: 23.9±0.5% vs. mean non-target occupancy: 25.36±0.17%, note that occupancy is slightly decreased in the target quadrant as animals entering the reward zone are teleported out; for visual task: p<0.001, target quadrant percentage occupancy: 59.6±1.15% vs. mean non-target occupancy: 13.5±0.38%, N = 5. (F) Normalized check rate as a function of distance away from the reward zone in radial bins for both trial types. Effect of distance from reward: F(14,112)  = 67.11, p<0.0001, p> 0.05 for effects of task type and interaction.</p