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On the role of subsecond dopamine release in conditioned avoidance.

Oleson EB, Cheer JF - Front Neurosci (2013)

Bottom Line: Current neuroscientific advances are providing new perspectives into this historical literature.Due to its well-established role in reinforcement processes and behavioral control, the mesolimbic dopamine system presented itself as a logical starting point in the search for neural correlates of avoidance and escape behavior.We recently demonstrated that phasic dopamine release events are inhibited by stimuli associated with aversive events but increased by stimuli preceding the successful avoidance of the aversive event.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Neurobiology, School of Medicine, University of Maryland Baltimore, MD, USA.

ABSTRACT
Using shock avoidance procedures to study conditioned behavioral responses has a rich history within the field of experimental psychology. Such experiments led to the formulation of the general concept of negative reinforcement and specific theories attempting to explain escape and avoidance behavior, or why animals choose to either terminate or prevent the presentation of an aversive event. For example, the two-factor theory of avoidance holds that cues preceding an aversive event begin to evoke conditioned fear responses, and these conditioned fear responses reinforce the instrumental avoidance response. Current neuroscientific advances are providing new perspectives into this historical literature. Due to its well-established role in reinforcement processes and behavioral control, the mesolimbic dopamine system presented itself as a logical starting point in the search for neural correlates of avoidance and escape behavior. We recently demonstrated that phasic dopamine release events are inhibited by stimuli associated with aversive events but increased by stimuli preceding the successful avoidance of the aversive event. The latter observation is inconsistent with the second component of the two-factor theory of avoidance and; therefore, led us propose a new theoretical explanation of conditioned avoidance: (1) fear is initially conditioned to the warning signal and dopamine computes this fear association as a decrease in release, (2) the warning signal, now capable of producing a negative emotional state, suppresses dopamine release and behavior, (3) over repeated trials the warning signal becomes associated with safety rather than fear; dopaminergic neurons already compute safety as an increase in release and begin to encode the warning signal as the earliest predictor of safety (4) the warning signal now promotes conditioned avoidance via dopaminergic modulation of the brain's incentive-motivational circuitry.

No MeSH data available.


Related in: MedlinePlus

The role of subsecond dopamine release during conditioned avoidance. (A) Changes in subsecond dopamine release observed in different response types observed in a single session. Representative color plots (left) and dopamine concentration traces (right) show avoidance (top), one-footshock escape (middle), and two-footshock escape (bottom) responses. Left, the y-axis represents the scan potential (Epp, V) applied to the electrode, the x-axis represents time, and the z-axis represents current. Inspection of the color plot allows for the identification of dopamine over time. Dopamine can be identified in the color plot by assessing for changes in current at the oxidation (+0.6V) and reduction (−0.2V) potentials for dopamine. Right, representative dopamine concentration traces plotted as a function of time with the inset showing the cyclic voltammograms for dopamine. Arrows indicate lever responses, lightning bolts indicate footshocks, trumpets indicate safety periods, levers + lights indicate warning signals. (B,C) Mean ± SEM dopamine concentration traces from all avoidance and escape responses. Maximal warning signal duration is representative by the light gray fill, subsequent safety periods are represented by the dark gray fill. (D) Maximal dopamine concentration evoked by warning signal presentation predicts conditioned avoidance. Originally published in Oleson et al. (2012).
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Figure 2: The role of subsecond dopamine release during conditioned avoidance. (A) Changes in subsecond dopamine release observed in different response types observed in a single session. Representative color plots (left) and dopamine concentration traces (right) show avoidance (top), one-footshock escape (middle), and two-footshock escape (bottom) responses. Left, the y-axis represents the scan potential (Epp, V) applied to the electrode, the x-axis represents time, and the z-axis represents current. Inspection of the color plot allows for the identification of dopamine over time. Dopamine can be identified in the color plot by assessing for changes in current at the oxidation (+0.6V) and reduction (−0.2V) potentials for dopamine. Right, representative dopamine concentration traces plotted as a function of time with the inset showing the cyclic voltammograms for dopamine. Arrows indicate lever responses, lightning bolts indicate footshocks, trumpets indicate safety periods, levers + lights indicate warning signals. (B,C) Mean ± SEM dopamine concentration traces from all avoidance and escape responses. Maximal warning signal duration is representative by the light gray fill, subsequent safety periods are represented by the dark gray fill. (D) Maximal dopamine concentration evoked by warning signal presentation predicts conditioned avoidance. Originally published in Oleson et al. (2012).

Mentions: To investigate whether subsecond dopamine release is altered by the presentation of a warning signal, we used fast-scan cyclic voltammetry to assess subsecond dopaminergic release events in the nucleus accumbens core during behavior maintained in an operant signaled shock avoidance procedure (Figure 2). In this task, a stimulus light was presented as a warning signal for 2 s prior to the delivery of recurring foot shocks. During this 2 s warning signal, a response lever was extended into an operant chamber which, if depressed, resulted in the immediate retraction of the lever and a 20 s safety period signaled by a tone (i.e., safety signal). Animals could initiate an avoidance response by pressing the lever during the 2 s warning signal, entirely preventing shock. Alternatively, once shocks commenced, animals could initiate an escape response by pressing the lever during this punishment period, terminating shock. This experimental design allowed us to assess dopamine signaling during warning signal presentation, safety periods and during two distinct behavioral responses—avoidance and escape. It is important to note that, regardless of the methodology used (i.e., operant or shuttle box), avoidance and escape responses are distinct. This distinction was originally noted in one of the first conditioned avoidance experiments using a shuttle box with a hurdle that separated a shock-free side from a shock side (Bolles, 1972). In this early study, Warner reported that animals would scramble under the hurdle during escape responses, but jump over the hurdle during avoidance responses (Warner, 1932). He further went on to study the unique behavioral responses produced independently by either the shock or the warning signal and found that the shock produced scampering reactions whereas the warning signal produced more calculated, coordinated reactions (Warner, 1932). In the operant signaled shock avoidance task used in our study, we also observed distinct escape and avoidance reactions. Early in training, during which only operant escape responses occur, we observed several unique behavior reactions to the shock: jumping up the wall, attacking the lever and freezing. Interestingly, an unintentional (i.e., not experimenter intended outcome) avoidance response sometimes emerged early in training as well. In certain instances animals attempted to avoid shock by grounding themselves. As in Watson's early finger avoidance study (1916), electrical continuity is only maintained if the rat is in contact between two electrodes or, in our case, two electrified bars comprising the grid floor of the operant chamber. Occasionally, animals balanced their hind paws on a single bar while propping their front paws on a side of the operant chamber, thereby breaking the continuity of the electrical circuit and avoiding footshock. As the contingencies of reinforcement were learned, however, these unintended behaviors begin to dissipate until consistently maintained avoidance and escape behaviors emerged. In our first study on this subject (Oleson et al., 2012), we only recorded dopamine from animals in our operant avoidance task after they began avoiding footshock in ~50% of trials. At this point in training, we visually observed one of two distinct behavioral reactions in response to warning signal presentation. When the animal successfully avoided footshock, an uninhibited motor sequence directed at the lever was observed upon presentation of the warning signal. When the animal escaped footshock, a hesitation—presumably a fear-induced freezing response—was observed upon presentation of the warning signal. While it is well established that amygdalar modulation of prefrontal cortical activity is critically important in the expression of conditioned fear (Davis, 1992; Morgan and LeDoux, 1995; Garcia et al., 1999), dopaminergic modulation of striatal input may be involved in the expression of the freezing response. The canonical view of the basal ganglia holds that the striatum outputs two parallel projections, the direct and indirect pathways, which either excite or inhibit behavioral activity, respectively. According to this canonical view, dopamine release events are theorized to promote behavioral activation by increasing activity along the direct pathway by acting on Gs coupled dopamine D1 receptors, whereas decreases in dopamine release may inhibit behavioral activation by increasing activity along the indirect pathway by acting on Gi/o coupled dopamine D2 receptors (DeLong and Wichmann, 2007). A recent optogenetic study supported this conceptualization by demonstrating that selective activation of striatal dopamine D1 receptor expressing neurons of the direct pathway promotes behavioral activation, while selective activation of striatal dopamine D2 receptor expressing neurons of the indirect pathway promotes freezing behavior (Kravitz et al., 2010). Thus, it is possible that dopamine may contribute to the expression of a freezing response, although additional optogentic studies should be conducted to directly assess for this possibility within the context of conditioned fear. It is also important to note that, rather than solely causing avoidance or freezing responses by activating dopamine D1 or D2 receptors, dopamine concentration changes within the striatum are thought to modulate converging amygdalar, hippocampal and prefrontal input (Floresco et al., 2001; Brady and O'Donnell, 2004) to control behavioral activation.


On the role of subsecond dopamine release in conditioned avoidance.

Oleson EB, Cheer JF - Front Neurosci (2013)

The role of subsecond dopamine release during conditioned avoidance. (A) Changes in subsecond dopamine release observed in different response types observed in a single session. Representative color plots (left) and dopamine concentration traces (right) show avoidance (top), one-footshock escape (middle), and two-footshock escape (bottom) responses. Left, the y-axis represents the scan potential (Epp, V) applied to the electrode, the x-axis represents time, and the z-axis represents current. Inspection of the color plot allows for the identification of dopamine over time. Dopamine can be identified in the color plot by assessing for changes in current at the oxidation (+0.6V) and reduction (−0.2V) potentials for dopamine. Right, representative dopamine concentration traces plotted as a function of time with the inset showing the cyclic voltammograms for dopamine. Arrows indicate lever responses, lightning bolts indicate footshocks, trumpets indicate safety periods, levers + lights indicate warning signals. (B,C) Mean ± SEM dopamine concentration traces from all avoidance and escape responses. Maximal warning signal duration is representative by the light gray fill, subsequent safety periods are represented by the dark gray fill. (D) Maximal dopamine concentration evoked by warning signal presentation predicts conditioned avoidance. Originally published in Oleson et al. (2012).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3675318&req=5

Figure 2: The role of subsecond dopamine release during conditioned avoidance. (A) Changes in subsecond dopamine release observed in different response types observed in a single session. Representative color plots (left) and dopamine concentration traces (right) show avoidance (top), one-footshock escape (middle), and two-footshock escape (bottom) responses. Left, the y-axis represents the scan potential (Epp, V) applied to the electrode, the x-axis represents time, and the z-axis represents current. Inspection of the color plot allows for the identification of dopamine over time. Dopamine can be identified in the color plot by assessing for changes in current at the oxidation (+0.6V) and reduction (−0.2V) potentials for dopamine. Right, representative dopamine concentration traces plotted as a function of time with the inset showing the cyclic voltammograms for dopamine. Arrows indicate lever responses, lightning bolts indicate footshocks, trumpets indicate safety periods, levers + lights indicate warning signals. (B,C) Mean ± SEM dopamine concentration traces from all avoidance and escape responses. Maximal warning signal duration is representative by the light gray fill, subsequent safety periods are represented by the dark gray fill. (D) Maximal dopamine concentration evoked by warning signal presentation predicts conditioned avoidance. Originally published in Oleson et al. (2012).
Mentions: To investigate whether subsecond dopamine release is altered by the presentation of a warning signal, we used fast-scan cyclic voltammetry to assess subsecond dopaminergic release events in the nucleus accumbens core during behavior maintained in an operant signaled shock avoidance procedure (Figure 2). In this task, a stimulus light was presented as a warning signal for 2 s prior to the delivery of recurring foot shocks. During this 2 s warning signal, a response lever was extended into an operant chamber which, if depressed, resulted in the immediate retraction of the lever and a 20 s safety period signaled by a tone (i.e., safety signal). Animals could initiate an avoidance response by pressing the lever during the 2 s warning signal, entirely preventing shock. Alternatively, once shocks commenced, animals could initiate an escape response by pressing the lever during this punishment period, terminating shock. This experimental design allowed us to assess dopamine signaling during warning signal presentation, safety periods and during two distinct behavioral responses—avoidance and escape. It is important to note that, regardless of the methodology used (i.e., operant or shuttle box), avoidance and escape responses are distinct. This distinction was originally noted in one of the first conditioned avoidance experiments using a shuttle box with a hurdle that separated a shock-free side from a shock side (Bolles, 1972). In this early study, Warner reported that animals would scramble under the hurdle during escape responses, but jump over the hurdle during avoidance responses (Warner, 1932). He further went on to study the unique behavioral responses produced independently by either the shock or the warning signal and found that the shock produced scampering reactions whereas the warning signal produced more calculated, coordinated reactions (Warner, 1932). In the operant signaled shock avoidance task used in our study, we also observed distinct escape and avoidance reactions. Early in training, during which only operant escape responses occur, we observed several unique behavior reactions to the shock: jumping up the wall, attacking the lever and freezing. Interestingly, an unintentional (i.e., not experimenter intended outcome) avoidance response sometimes emerged early in training as well. In certain instances animals attempted to avoid shock by grounding themselves. As in Watson's early finger avoidance study (1916), electrical continuity is only maintained if the rat is in contact between two electrodes or, in our case, two electrified bars comprising the grid floor of the operant chamber. Occasionally, animals balanced their hind paws on a single bar while propping their front paws on a side of the operant chamber, thereby breaking the continuity of the electrical circuit and avoiding footshock. As the contingencies of reinforcement were learned, however, these unintended behaviors begin to dissipate until consistently maintained avoidance and escape behaviors emerged. In our first study on this subject (Oleson et al., 2012), we only recorded dopamine from animals in our operant avoidance task after they began avoiding footshock in ~50% of trials. At this point in training, we visually observed one of two distinct behavioral reactions in response to warning signal presentation. When the animal successfully avoided footshock, an uninhibited motor sequence directed at the lever was observed upon presentation of the warning signal. When the animal escaped footshock, a hesitation—presumably a fear-induced freezing response—was observed upon presentation of the warning signal. While it is well established that amygdalar modulation of prefrontal cortical activity is critically important in the expression of conditioned fear (Davis, 1992; Morgan and LeDoux, 1995; Garcia et al., 1999), dopaminergic modulation of striatal input may be involved in the expression of the freezing response. The canonical view of the basal ganglia holds that the striatum outputs two parallel projections, the direct and indirect pathways, which either excite or inhibit behavioral activity, respectively. According to this canonical view, dopamine release events are theorized to promote behavioral activation by increasing activity along the direct pathway by acting on Gs coupled dopamine D1 receptors, whereas decreases in dopamine release may inhibit behavioral activation by increasing activity along the indirect pathway by acting on Gi/o coupled dopamine D2 receptors (DeLong and Wichmann, 2007). A recent optogenetic study supported this conceptualization by demonstrating that selective activation of striatal dopamine D1 receptor expressing neurons of the direct pathway promotes behavioral activation, while selective activation of striatal dopamine D2 receptor expressing neurons of the indirect pathway promotes freezing behavior (Kravitz et al., 2010). Thus, it is possible that dopamine may contribute to the expression of a freezing response, although additional optogentic studies should be conducted to directly assess for this possibility within the context of conditioned fear. It is also important to note that, rather than solely causing avoidance or freezing responses by activating dopamine D1 or D2 receptors, dopamine concentration changes within the striatum are thought to modulate converging amygdalar, hippocampal and prefrontal input (Floresco et al., 2001; Brady and O'Donnell, 2004) to control behavioral activation.

Bottom Line: Current neuroscientific advances are providing new perspectives into this historical literature.Due to its well-established role in reinforcement processes and behavioral control, the mesolimbic dopamine system presented itself as a logical starting point in the search for neural correlates of avoidance and escape behavior.We recently demonstrated that phasic dopamine release events are inhibited by stimuli associated with aversive events but increased by stimuli preceding the successful avoidance of the aversive event.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Neurobiology, School of Medicine, University of Maryland Baltimore, MD, USA.

ABSTRACT
Using shock avoidance procedures to study conditioned behavioral responses has a rich history within the field of experimental psychology. Such experiments led to the formulation of the general concept of negative reinforcement and specific theories attempting to explain escape and avoidance behavior, or why animals choose to either terminate or prevent the presentation of an aversive event. For example, the two-factor theory of avoidance holds that cues preceding an aversive event begin to evoke conditioned fear responses, and these conditioned fear responses reinforce the instrumental avoidance response. Current neuroscientific advances are providing new perspectives into this historical literature. Due to its well-established role in reinforcement processes and behavioral control, the mesolimbic dopamine system presented itself as a logical starting point in the search for neural correlates of avoidance and escape behavior. We recently demonstrated that phasic dopamine release events are inhibited by stimuli associated with aversive events but increased by stimuli preceding the successful avoidance of the aversive event. The latter observation is inconsistent with the second component of the two-factor theory of avoidance and; therefore, led us propose a new theoretical explanation of conditioned avoidance: (1) fear is initially conditioned to the warning signal and dopamine computes this fear association as a decrease in release, (2) the warning signal, now capable of producing a negative emotional state, suppresses dopamine release and behavior, (3) over repeated trials the warning signal becomes associated with safety rather than fear; dopaminergic neurons already compute safety as an increase in release and begin to encode the warning signal as the earliest predictor of safety (4) the warning signal now promotes conditioned avoidance via dopaminergic modulation of the brain's incentive-motivational circuitry.

No MeSH data available.


Related in: MedlinePlus