Summary: Decoding the brain’s knack for distinguishing new from familiar is a challenge that has puzzled scientists. New research brings clarity to “visual recognition memory” (VRM), the process that ensures we prioritize what’s most important in what we see.
The study reconciles contradictory findings by revealing that brief, pronounced neural spikes signify familiarity, surrounded by a larger lull in activity. This offers insight into the brain’s rapid identification and suppression mechanisms for familiar stimuli.
Key Facts:
- VRM allows us to quickly identify familiar things in our environment, focusing our attention on what’s new or unexpected.
- Past research has shown conflicting neural activity patterns upon viewing familiar stimuli: decreased activity versus sharp jumps (VEPs) in activity.
- This study explains the contradiction, revealing that VEPs are brief spikes within an overarching neural activity reduction, signifying quick familiarity recognition.
Source: Picower Institute for Learning and Memory
Because figuring out what is new and what is familiar in what we see is such a critically important ability for prioritizing our attention, neuroscientists have spent decades trying to figure out how our brains are typically so good at it. Along the way they’ve made key observations that seem outright contradictory, but a new study shows that the mystifying measures are really two sides of the same coin, paving the way for a long-sought understanding of “visual recognition memory” (VRM).
VRM is the ability to quickly recognize the familiar things in scenes, which can then be de-prioritized so that we can focus on the new things that might be more important in a given moment. Imagine you walk into your home office one evening to respond to an urgent, late email. There you see all the usual furniture and equipment—and a burglar. VRM helps ensure that you’d focus on the burglar, not your book shelves or your desk lamp.
“Yet we do not yet have a clear picture of how this foundational form of learning is implemented within the mammalian brain,” wrote Picower Professor Mark Bear and fellow authors of the new study in the Journal of Neuroscience.
As far back as 1991 researchers found that when animals viewed something familiar, neurons in cortex, or outer layer of their brain, would be less activated than if they saw something new (two of that study’s authors later became Bear’s colleagues at MIT, Picower Professor Earl K. Miller and Doris and Don Berkey Professor Bob Desimone).
But in 2003, Bear’s lab happened to observe the opposite: Mice would actually show a sharp jump in neural activity in the primary visual region of the cortex when a familiar stimulus was flashed in front of the animal. This spike of activity is called a “visually evoked potential” (VEP), and Bear’s lab has since shown that increases in the VEPs are solid indicators of VRM.
The findings in the new study, led by former Bear Lab postdocs Dustin Hayden and Peter Finnie, explain how VEPs increase even amid an overall decline in neural response to familiar stimuli (as seen by Miller and Desimone), Bear said. They also explain more about the mechanisms underlying VRM – the momentary increase of a VEP may be excitation that recruits inhibition, thereby suppressing activity overall.
New understanding
Bear’s lab evokes VEPs by showing mice a black-and-white striped grating in which the stripes periodically switch their shade so that the pattern appears to reverse. Over several days as mice view this stimulus pattern, the VEPs increase, a reliable correlate of the mice becoming familiar with—and less interested in—the pattern.
For 20 years Bear’s lab has been investigating how the synapses involved in VRM change by studying a phenomenon they’ve dubbed “stimulus-selective response plasticity” (SRP).
Early studies had suggested that SRP occurs among excitatory neurons in layer 4 of the visual cortex and specifically might require the molecular activation of their NMDA receptors.
The lab had seen that knocking out the receptors across the visual cortex prevented the increase in VEPs and therefore SRP, but a follow-up in 2019 found that knocking them out just in layer 4 had no effect. So, in the new study they decided to study VEPs, SRP and VRM across the whole visual cortex, layer by layer, in search of how it all works.
What they found was that many of the hallmarks of VRM, including VEPs, occur in all layers of the cortex but that it seemed to depend on NMDA receptors on a population of excitatory neurons in layer 6, not layer 4. This is an intriguing finding, the authors said, because those neurons are well connected to the thalamus (a deeper brain region that relays sensory information) and to inhibitory neurons in layer 4, where they had first measured VEPs.
They also measured changes in brain waves in each layer that confirmed a previous finding that when the stimulus pattern is new, the prevailing brain wave oscillations are in a higher “gamma” frequency that depends on one kind of inhibitory neuron, but as it becomes more familiar, the oscillations shift toward a lower “beta” frequency that depends on a different inhibitory population.
A short spike amid a long lull
The team’s rigorous and precise electrophysiology recordings of neural electrical activity in the different layers also revealed a potential resolution to the contradiction between VEPs and the measures of labs like that of Miller and Desimone.
“What this paper reveals is that everybody is right,” Bear quipped.
How so? The new data show that VEPs are very pronounced but transient spikes of neural electrical activity that occur amid a broader, overall lull of activity. Previous studies have reflected only the overall decrease because they have not had the temporal resolution to detect the brief spike. Bear’s team, meanwhile, has seen the VEPs for years but didn’t necessarily focus on the surrounding lull.
The new evidence suggests that what’s happening is that the VEP is a sign of the activity of the brain quickly recognizing a familiar stimulus and then triggering an inhibition of activity related to it.
“What I think is exciting about this is that it suddenly sheds light on the mechanism, because it’s not that the encoding of familiarity is explained by the depression of excitatory synapses,” Bear said.
“Rather, it seems to be accounted for by the potentiation of excitatory synapses on to neurons that then recruit inhibition in the cortex.”
Even as it advances that understanding of how VRM arises, the study still leaves open questions including the exact circuits involved. For instance, the exact contribution of the layer 6 circuit neurons is not yet clear, Bear said. And so, the quest goes on.
In addition to Hayden, Finnie and Bear, the paper’s other authors are Aurore Thomazeau, Alyssa Li and Samuel Cooke.
Funding: The National Eye Institute of the National Institutes of Health, The Picower Institute for Learning and Memory and The JPB Foundation funded the study.
About this visual memory research news
Author: David Orenstein
Source: Picower Institute for Learning and Memory
Contact: David Orenstein – Picower Institute for Learning and Memory
Image: The image is credited to Neuroscience News
Original Research: Closed access.
“Electrophysiological signatures of visual recognition memory across all layers of mouse V1” by Mark Bear et al. Journal of Neuroscience
Abstract
Electrophysiological signatures of visual recognition memory across all layers of mouse V1
In mouse primary visual cortex (V1), familiar stimuli evoke significantly altered responses when compared to novel stimuli. This stimulus-selective response plasticity (SRP) was described originally as an increase in the magnitude of visual evoked potentials (VEPs) elicited in layer 4 (L4) by familiar phase-reversing grating stimuli.
SRP is dependent on NMDA receptors (NMDAR) and has been hypothesized to reflect potentiation of thalamocortical synapses in L4. However, recent evidence indicates that the synaptic modifications that manifest as SRP do not occur on L4 principal cells.
To shed light on where and how SRP is induced and expressed in male and female mice, the present study had three related aims: (1) to confirm that NMDAR are required specifically in glutamatergic principal neurons of V1, (2) to investigate the consequences of deleting NMDAR specifically in L6, and (3) to use translaminar electrophysiological recordings to characterize SRP expression in different layers of V1.
We find that knockout of NMDAR in L6 principal neurons disrupts SRP. Current-source density analysis of the VEP depth profile shows augmentation of short latency current sinks in layers 3, 4 and 6 in response to phase reversals of familiar stimuli.
Multiunit recordings demonstrate that increased peak firing occurs in response to phase reversals of familiar stimuli across all layers, but that activity between phase reversals is suppressed.
Together, these data reveal important aspects of the underlying phenomenology of SRP and generate new hypotheses for the expression of experience-dependent plasticity in V1.
