Pavlovian Fear Conditioning Is More than You Think It Is

Abstract

A common neuroscience application of Pavlovian fear conditioning is to manipulate neuron-type activity, pair a cue with foot shock, then measure cue-elicited freezing in a novel context. If the manipulation reduces freezing, the neuron type is implicated in Pavlovian fear conditioning. This application reduces Pavlovian fear conditioning to a single concept. In this Viewpoint, I describe experiments supporting the view that Pavlovian fear conditioning refers to three distinct concepts: procedure, process, and behavior. An experimenter controls procedure, observes behavior, but infers process. Distinguishing these concepts is essential because: (1) a shock-paired cue can engage numerous processes and behaviors; (2) experimenter decisions about procedure influence the processes engaged and behaviors elicited; and (3) many processes are latent, imbuing the cue with properties that only manifest outside of the original conditioning setting. This means we could understand the complete neural basis of freezing, yet know little about the neural basis of fear. Neuroscientists can choose to use a variety of procedures to study a diversity of processes and behaviors. Manipulating neuron-type activity in multiple procedures can reveal specific, general, or complex neuron-type contributions to cue-elicited processes and behaviors. The results will be a broader and more detailed neural basis of fear with greater relevance to the spectrum of symptoms defining anxiety and stressor-related disorders.

Figure 1.

Procedure, process, and behavior in Pavlovian fear conditioning. A, Schematic of Pavlovian fear conditioning in which a single procedure (gray) engages a single internal process (white), to elicit a single behavioral outcome (freezing, red). B, Schematic of Pavlovian fear conditioning in which different procedures (black vs gray), engage unique and overlapping processes (abstract patterns), to elicit (triangles) or inhibit (circles) a suite of behaviors (red represents freezing; cyan represents reward seeking; green represents running).

Figure 2.

PubMed search for behavioral outcomes in neuroscience-publishing journals in the last decade. A PubMed search was performed on July 14, 2023 for 13 behavioral outcomes (listed on x axis). The search terms were the behavioral outcome (any field) and fear (title/abstract). The search was restricted to the last 10 years and to 27 behavioral-neuroscience publishing journals: Behavioral Neuroscience, Behavioural Brain Research, Biological Psychiatry, Cell, Cell Reports, Communications Biology, Current Biology, eLife, eNeuro, European Journal of Neuroscience, Frontiers in Behavioral Neuroscience, Journal of Neuroscience, Learning & Memory, Molecular Psychiatry, Nature, Nature Communications, Nature Neuroscience, Neurobiology of Learning and Memory, Neuron, Neuropharmacology, Neuropsychopharmacology, Neuroscience, Physiology & Behavior, Psychopharmacology, Science, Science Advances, and Translational Psychiatry. The number of search results is reported for each behavioral outcome (y axis). The specific number of results is indicated for behavioral outcomes returning <100.

Figure 3.

Interpreting effects of neuron-type manipulation with procedure, process, and behavior. A, Equating procedure, process, and behavior can result in claims that Pavlovian fear conditioning failed to occur when a neuron-type manipulation abolishes a conditioned behavior (red represents freezing). B, Schematic of Pavlovian fear conditioning in which different procedures (black vs gray), engage unique and overlapping processes (abstract patterns), to elicit (triangles) or inhibit (circles) a suite of behaviors (red represents freezing; cyan represents reward seeking; green represents running) as well as latent processes manifesting outside of the original conditioning setting. A neuron-type manipulation that disrupts the process eliciting freezing may leave other processes and behavioral outcomes intact. C, Schematic same as in B. A neuron-type manipulation that disrupts the process eliciting running may leave other processes and behavioral outcomes intact.

Figure 4.

Using procedure to link processes and behaviors to neuron types. Hypothetical results of studies using 6 different Pavlovian fear conditioning procedures (rows 1-6) that assess 4 distinct behaviors (red represents freezing; cyan represents reward seeking; green represents running; purple represents rearing) and 2 latent processes (gray represents promote avoidance; black represents serve as punisher). The 10 columns (A-J) represent 10 distinct neuron types nested in distinct brain regions. Each of the 60 cells (6 rows × 10 columns) represents a single experiment in which neuron-type activity is inhibited during a specific procedure (e.g., in cell F6, neuron Type F is inhibited during a conditioned punishment procedure). Filled cells represent that inhibiting neuron-type activity disrupts behavior or process (e.g., inhibiting activity of neuron Types A, G, I, and J disrupt cued freezing). Pattern across procedures can reveal specific (A–F), general (G and H), or complex (I and J) neuron-type contributions to processes and behaviors.