Parsing neural circuits of fear learning and extinction across basic and clinical neuroscience: towards better translation

Background: The use of Machine Learning (ML) is witnessing an exponential growth in the field of artificial intelligence (AI) and neuroscience, in particular in subdisciplines such as Systems Neuroscience (SN), as a viable alternative to the use of classical statistical techniques. The combination of this interconnection allows a more detailed study of algorithms and neural circuits that emulate core cognitive processes. ML toolbox includes algorithms that are suited to solving problems of classification, regression, clustering and anomaly detection. Objective: The aim of the present opinion was to exemplify the contribution of ML in the field of SN in three different fields: 1) cognitive modelling; 2) neuroimaging; 3) analysis of clinical datasets. Method: We gathered evidence from the relevant literature related to the interaction between neuroscience and AI and the impact of ML in SN. Results : ML is specifically suited to the analysis of large clinical neuroscience datasets. Experimental results in neuroscience are hard to replicate for a number of reasons and ML may contribute to attenuating these replicability issues via the ubiquitous use of cross-validation procedures. While ML modelling is primarily focused on prediction accuracy, one of the drawbacks in ML is the opacity of various algorithms that resist to intuitive understanding. Conclusions: Future avenues of research have already been traced and include increased interpretability of currently opaque ML models functioning and causal analysis. Causal analysis is intended to distinguish between spurious associations and cause-effect relationship and is a primary interest in both clinical medicine and basic neuroscience.

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The gastrin-releasing peptide regulates stress-enhanced fear and dopamine signaling

10.1101/2020.12.31.424996 ◽

2021 ◽

Author(s):

Yoshikazu Morishita ◽

Ileana Fuentes ◽

John Favate ◽

Ko Zushida ◽

Akinori Nishi ◽

...

Keyword(s):

Basolateral Amygdala ◽

Neural Circuits ◽

Cell Types ◽

Fear Extinction ◽

Fear Learning ◽

Gastrin Releasing Peptide ◽

The Core ◽

Molecular Identity ◽

Dopamine Signaling ◽

Organizational Logic

AbstractFear extinction is an adaptive behavioral process critical for organism’s survival, but deficiency in extinction may lead to PTSD. While the amygdala and its neural circuits are critical for fear extinction, the molecular identity and organizational logic of cell types that lie at the core of these circuits remain unclear. Here we report that mice deficient for amygdala-enriched gastrin-releasing peptide gene (Grp-/-) exhibit enhanced neuronal activity in the basolateral amygdala (BLA) and stronger fear conditioning, as well as deficient extinction in stress-enhanced fear learning (SEFL). rAAV2-retro-based tracing combined with visualization of the GFP knocked in the Grp gene showed that BLA receives GRPergic or conditioned stimulus projections from the indirect auditory thalamus-to-auditory cortex pathway, ventral hippocampus and ventral tegmental area. Transcription of dopamine-related genes was decreased in BLA of Grp-/- mice following SEFL extinction recall, suggesting that the GRP may mediate fear extinction regulation by dopamine.Impact statementMice deficient for the amygdala-enriched gastrin-releasing peptide gene are susceptible to stress-enhanced fear, a behavioral protocol with relevance to PTSD, and show a decrease in dopamine-related gene transcription.

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Nucleus Basalis links sensory stimuli with delayed reinforcement to support learning

10.1101/663211 ◽

2019 ◽

Author(s):

W. Guo ◽

D.B. Polley

Keyword(s):

Basal Forebrain ◽

Neural Circuits ◽

Cortical Plasticity ◽

Cholinergic Neurons ◽

Nucleus Basalis ◽

Fear Learning ◽

Delayed Reinforcement ◽

Sensory Stimuli ◽

Sensory Inputs ◽

Cholinergic Basal Forebrain

SummaryLinking stimuli with delayed reinforcement requires neural circuits that can bridge extended temporal gaps. Auditory cortex (ACx) circuits reorganize to support auditory fear learning, but only when afferent sensory inputs temporally overlap with cholinergic reinforcement signals. Here we show that mouse ACx neurons rapidly reorganize to support learning, even when sensory and reinforcement cues are separated by a long gap. We found that cholinergic basal forebrain neurons bypass the temporal delay through multiplexed, short-latency encoding of sensory and reinforcement cues. At the initiation of learning, cholinergic neurons in Nucleus Basalis increase responses to conditioned sound frequencies and increase functional connectivity with ACx. By rapidly scaling up responses to sounds that predict reinforcement, cholinergic inputs jump the gap to align with bottom-up sensory traces and support associative cortical plasticity.

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Neural Circuits Mediating Fear Learning and Extinction

Advances in Neurobiology - Systems Neuroscience ◽

10.1007/978-3-319-94593-4_2 ◽

2018 ◽

pp. 35-48 ◽

Cited By ~ 8

Author(s):

Roger Marek ◽

Pankaj Sah

Keyword(s):

Neural Circuits ◽

Fear Learning

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Psychological Processes in Chronic Pain: Influences of Reward and Fear Learning as Key Mechanisms – Behavioral Evidence, Neural Circuits, and Maladaptive Changes

Neuroscience ◽

10.1016/j.neuroscience.2017.08.051 ◽

2018 ◽

Vol 387 ◽

pp. 72-84 ◽

Cited By ~ 6

Author(s):

Frauke Nees ◽

Susanne Becker

Keyword(s):

Chronic Pain ◽

Neural Circuits ◽

Fear Learning ◽

Psychological Processes ◽

Behavioral Evidence

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Fear conditioning and the basolateral amygdala

F1000Research ◽

10.12688/f1000research.21201.1 ◽

2020 ◽

Vol 9 ◽

pp. 53 ◽

Cited By ~ 4

Author(s):

Yajie Sun ◽

Helen Gooch ◽

Pankaj Sah

Keyword(s):

Fear Conditioning ◽

Basolateral Amygdala ◽

Neural Circuits ◽

Long Term Potentiation ◽

Fear Learning ◽

Pavlovian Fear Conditioning ◽

Defensive Responses ◽

Laboratory Rodents ◽

Term Potentiation

Fear is a response to impending threat that prepares a subject to make appropriate defensive responses, whether to freeze, fight, or flee to safety. The neural circuits that underpin how subjects learn about cues that signal threat, and make defensive responses, have been studied using Pavlovian fear conditioning in laboratory rodents as well as humans. These studies have established the amygdala as a key player in the circuits that process fear and led to a model where fear learning results from long-term potentiation of inputs that convey information about the conditioned stimulus to the amygdala. In this review, we describe the circuits in the basolateral amygdala that mediate fear learning and its expression as the conditioned response. We argue that while the evidence linking synaptic plasticity in the basolateral amygdala to fear learning is strong, there is still no mechanism that fully explains the changes that underpin fear conditioning.

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