Prevalence of a Concept Changes How We View It

What's the science?

The term ‘creep’ describes the (sometimes unwanted) expansion of something over time, like the mission of a company or features of a product. It can also apply to abstract concepts such as aggression, a term which has expanded over time to apply to less aggressive acts than it used to. Many studies from neuroscience have taught us that humans judge things compared to their recent context (i.e. if there is less aggression, then an aggressive act may be seen as more aggressive than it did in the past). This can be a problem when the goal is to reduce the prevalence of something; if you are succeeding at getting rid of something bad, but keep calling a wider range of things bad, how will you ever know that you are making progress? This week in Science, Levari and colleagues investigate this phenomenon of ‘prevalence-induced concept change’ in humans.

How did they do it?

Participants were shown stimuli and were asked to determine whether a stimulus was an example of a particular concept. In the first experiment, participants were shown 1000 dots that varied from purple to blue. Over time, the prevalence of blue dots was reduced and participants’ responses were analyzed to see whether they called a wider range of colors blue (i.e. whether the concept expanded). A second condition with a stable prevalence of these concepts was also carried out as a control (i.e. the number of blue and purple dots was consistent over time). The authors then performed several replication experiments to test whether a) telling the participant that the prevalence would change, b) instructing them be consistent or c) changing the rate of reduction in prevalence would affect their behavior. They also tested what effect increasing the prevalence of a certain stimulus (i.e. increasing blue dots or purple dots) would have. They then repeated the experiments above with a more complex stimulus: faces that varied from non-threatening to very threatening. Finally, they performed another similar experiment in which they asked participants to judge the abstract concept of whether proposed scientific experiments were ethical or not. Participants were shown proposals for scientific studies and asked to determine whether they should be allowed.

What did they find?

Over time, participants were more likely to report a dot as being blue after the prevalence of the blue dots decreased. This result was robust, and persisted even after participants were told that the prevalence would decrease, and after they were instructed to be consistent. A more rapid decline in the prevalence of blue dots did not change this effect. Increasing the prevalence of the blue dots resulted in participants being less likely to report blue dots towards the end of the trials, demonstrating a reversal of this effect. When stimuli were changed to faces (a range of non-threatening to very threatening) the same effect was observed: participants reported more faces as threatening after a reduction in the prevalence of threatening faces. This also applied to the concept of judging whether a scientific proposal is ethical or not: the fewer unethical proposals presented, the more likely a participant was to reject a proposal as unethical. These behavioral results demonstrate a robust effect of “prevalence-induced concept change” that can apply to a variety of concepts.

What's the impact?

This study demonstrates how widespread prevalence effects can be, ranging from simple color judgements to complex ethical judgments. Humans are likely to expand the definition of concepts when they become less prevalent. These findings have important implications for institutions that make decisions that need to stay consistent over time, like medicine or law enforcement. This phenomenon may help to explain why individuals fail to recognize progress, even as some problems really do get better.

Levari et al., Prevalence-induced concept change in human judgement. Science (2018). Access the original scientific publication here.

Dopamine is Involved in Switching from Feelings of Fear to Safety

What's the science?

Moving on from negative experiences requires identifying when it is no longer appropriate to be fearful. Understanding the neurobiology of fear is important for disorders like post-traumatic stress disorder. Dopamine neurons originating in the brainstem (the ventral tegmental area) release dopamine in limbic (i.e. emotional) regions of the brain and are involved in signalling when outcomes are better than expected. Therefore, these neurons may be involved in transitioning from ‘fear responding’ to ‘safety’. This week in Nature Communications Luo and colleagues investigate how midbrain dopamine neurons are involved in extinguishing fear responses.

How did they do it?

Rats were exposed to a foot shock paired with an auditory stimulus. One day later, rats were exposed to the auditory stimulus (without foot shock) and underwent an ‘extinction learning’ session where the freezing (i.e. fear) response to the auditory stimulus is reduced or unlearned over time. Another day later, they were cued with the auditory stimulus again to see whether the fear response was completely gone. They used an optogenetic approach to silence the activity of midbrain dopamine neurons in these rats during the precise time period of extinction learning when the expected shock did not occur, to see whether midbrain dopamine was responsible for the extinction of fear memories. They then tested how extinction is occurring on a molecular level using optogenetics combined with immunohistochemistry.

What did they find?

Control mice demonstrated reduced freezing responses typical of fear extinction, while mice with silenced midbrain dopamine neuron firing showed a reduction in fear extinction (i.e. they still had freezing responses despite the extinction training). Since the phosphorylation of MAP kinase (MAPK) has been shown to mediate fear extinction, they tested to see whether levels of phosphorylated MAPK were lower in the rats who lacked fear extinction. They found, using immunohistochemistry, that MAPK levels were lower during the extinction training in mice whose dopamine neurons were inhibited. This suggests that dopamine neuron activity engages this molecular process during fear extinction. They then examined whether dopamine release has different effects on fear extinction learning at different release sites. They found that specifically inhibiting nerve terminals in the nucleus accumbens (a brain region involved in reward) reduced fear extinction, whereas inhibiting terminals in the ventromedial prefrontal cortex enhanced fear extinction (i.e. rats more effectively reduced their fear response). This suggests that nucleus accumbens dopamine mediates (i.e. promotes) fear extinction, while dopamine in the ventromedial prefrontal cortex opposes fear extinction. Using retrograde tracers, they found that the projections to the shell of the nucleus accumbens, rather than the core of the nucleus accumbens, mediated fear extinction.

What's the impact?

This is the first study to demonstrate that dopamine activity that occurs when an expected aversive outcome does not occur is involved in reducing fear responses to a fearful stimulus. We now know that midbrain dopamine neurons projecting to the nucleus accumbens play a critical role in overcoming fear responses when they are no longer appropriate (i.e. safe situations). Understanding the biology of fear extinction provides a better understanding of detrimental fear responses in anxiety disorders.

Luo et al., A dopaminergic switch for fear to safety transitions. Nature Communications (2018). Access the original scientific publication here.

A New Cell Type in the Hippocampus Contributes to Sharp Waves Involved in Memory

What's the science?

The dentate gyrus and the CA3 are two important regions involved in memory in the hippocampus. The dentate gyrus separates out incoming signals from the cortex and relays patterns of information to the CA3 pyramidal cells via thorny “mossy fiber” projections. Cues can then reactivate this pattern of information in the CA3 cells (also known as pattern completion). The way in which CA3 neurons are able to reactivate the neurons encoding a memory involves recurrent network activity, however the details are not well understood. Understanding differences in cell types within the CA3 of the hippocampus could improve our understanding of this process of reactivating memories. This week in Nature Neuroscience, Hunt and colleagues examine different pyramidal cell types within the CA3 and their activity patterns during sharp waves (i.e. spontaneous reactivation of memory neurons) to understand their role in the “replay” of memory.

How did they do it?

They performed whole-cell patch-clamp on hippocampal tissue slices from mice to assess how the neurons in the CA3 would fire in response to current injection (to cause action potential firing). They then examined the structural and molecular properties of these neurons to see how cell types within the CA3 differed. Next, they used a transgenic mouse line and optogenetics to express light activated channels in mossy fiber axons projecting to CA3 cells from the dentate gyrus. They activated these fibers and measured excitatory post-synaptic currents to map input from dentate gyrus to different pyramidal cells within the CA3. In mice, they measured activity (local field potentials and multi-unit activity) of different labelled pyramidal cells during “sharp wave” events, which are the spontaneous neuron firing events in the CA3, known to be important for memory. The goal was to understand how different pyramidal cells and their firing properties contribute to memory. They used optogenetic activation of cholinergic neurons, which are known to regulate memory in the hippocampus, to test how different pyramidal cell types responded to cholinergic modulation. Lastly, they constructed an “attractor network model” to show how these different cell types contribute to network dynamics in the hippocampus during memory replay.

What did they find?

There were two types of responses from neurons within the CA3 after current injection: neurons that fired in a regular pattern and neurons that fired in a “burst” pattern. The regular firing neurons had thorny spines as expected of CA3 cells, however the burst firing neurons did not have thorny spines (i.e athorny cells). Using a clustering approach, the two cell types were segregated based on their different electrophysiological and structural properties. Using optogenetic activation of mossy fibers, they found that mossy fibers project to regular thorny neurons but not to athorny burst firing neurons in the CA3. However, both thorny and athorny neurons were excited by recurrent activation (i.e. by neurons nearby).

In mice, they measured neuron activity during sharp wave events, which had two phases: an initial ramp phase followed by an exponential increase in firing. They measured properties of firing of the two cell types and found that they behaved differently: thorny cells contribute to initial single spike activity and this spiking peaked during the exponential phase of the sharp wave event, while athorny cells weakly increased their single spike rate during the ramp and exponential phase of the sharp wave event. Athorny neurons contributed more to the complex burst firing (as opposed to single unit firing) component of sharp wave events. Optogenetic activation of cholinergic cells abolished sharp wave events, indicating that sharp waves are regulated by acetylcholine (a neurotransmitter that modulates activity). Further, activation of cholinergic neurons downregulated the burst firing of the athorny pyramidal cells, suggesting that low acetylcholine levels may facilitate the reactivation of pyramidal cells during the “replay” of memory during sharp wave events. Using an “attractor network model” they found that burst firing (driven by athorny cells) were important for evoking sharp wave events, suggesting that these newly defined cells are crucial for memory replay.

What's the impact?

This is the first study to demonstrate that a new “athorny” cell type in the CA3 region of the hippocampus is involved in memory. This new athorny neuron plays a role in burst firing associated with “sharp wave” events that are important for the reactivation of memory (i.e. memory replay). Understanding the cell types involved in memory circuits in the hippocampus is crucial to understanding how memory is encoded and retrieved.

Hunt et al., A novel pyramidal cell type promotes sharp-wave synchronization in the hippocampus. Nature Neuroscience (2018). Access the original scientific publication here.