Effects Of Fear Conditioning Research Articles

Sexually Dimorphic Expression of Fear-conditioned Analgesia in Rats and Associated Alterations in the Endocannabinoid System in the Periaqueductal Grey

The endocannabinoid system within the periaqueductal grey (PAG) has been implicated in fear-conditioned analgesia (FCA), the profound suppression of pain upon re-exposure to a context previously paired with an aversive stimulus. Since the endocannabinoid and nociceptive systems exhibit sexual dimorphism, the aim of the present study was to assess possible sex differences in the expression of FCA, fear in the presence of nociceptive tone, and associated sex-dependent alterations in the endocannabinoid system within the PAG. Male and female Sprague-Dawley rats received footshock (10 × 1s; 0.4 mA; every 60 s) or no-footshock in a conditioning arena and 23.5 h later received intraplantar injection of formalin (2.5%) under brief isoflourane anaesthetic into the right hind paw. Nociceptive and fear-related behaviours were assessed 30 min later. Levels of endocannabinoids, N-acylethanolamines and neurotransmitters in the PAG were assessed by LC–MS/MS and expression of endocannabinoid system-related proteins by Western immunoblotting. Male, but not female, rats exhibited robust FCA and greater expression of fear-related behaviours than females. Fear-conditioned formalin-treated males, but not females, had higher levels of N-oleoylethanolamine (OEA) and γ-aminobutyric acid (GABA) in the PAG, compared with non-fear-conditioned controls. There was no effect of fear conditioning on the levels of FAAH or CB1 receptor expression (CB1R) in the PAG of male or female formalin-treated rats. Non-fear-conditioned females had higher levels of CB1R and PPARγ expression than non-fear-conditioned male counterparts. In summary, our results provide evidence of sexual dimorphism in the expression of FCA and fear-related behaviours, and associated alterations in components of the endocannabinoid system and GABA within the PAG.

Diminished Fear Extinction in Adolescents Is Associated With an Altered Somatostatin Interneuron–Mediated Inhibition in the Infralimbic Cortex

BackgroundRodents and humans show an attenuation of fear extinction during adolescence, which coincides with the onset of several psychiatric disorders. Although the ethological relevance and the underlying mechanism are largely unknown, the suppression of fear extinction during adolescence is associated with a diminished plasticity in the glutamatergic neurons of the infralimbic medial prefrontal cortex, a brain region critical for fear extinction. Given the putative effect of synaptic inhibition on glutamatergic neuron activity, we studied whether gamma-aminobutyric acidergic neurons in the infralimbic medial prefrontal cortex are involved in the suppression of fear extinction during adolescence. MethodsWe assessed membrane and synaptic properties in parvalbumin-positive interneurons (PVINs) and somatostatin-positive interneurons (SSTINs) in male preadolescent, adolescent, and adult mice. The effect of fear conditioning and extinction on PVIN-pyramidal neuron and SSTIN-pyramidal neuron synapses in male preadolescent, adolescent, and adult mice was evaluated using an optogenetic approach. ResultsThe development of the membrane excitability of PVINs is delayed and reaches maturity only by adulthood, while the SSTIN membrane properties are developed early and remain stable during development from preadolescence to adulthood. Although the synaptic inhibition mediated by PVINs undergoes a protracted development, it does not exhibit a fear behavior–specific plasticity. However, the synaptic inhibition mediated by SSTINs undergoes an adolescence-specific enhancement, and this increased inhibition is suppressed by fear learning but is not restored by extinction training. This altered plasticity during adolescence overlapped with a reduction in calcium-permeable glutamate receptors in SSTINs. ConclusionsThe adolescence-specific plasticity in the SSTINs might play a role in fear extinction suppression during adolescence in mice.

Effects of cued and contextual fear on sleep in DBA/2J mice

Fear conditioning alters sleep, with the most consistent effect being significant reductions in rapid eye movement sleep (REM). DBA/2 (D2) mice show behavioral signs of anxiety, respond greater to shock training, and potentially behave differently in cued and contextual fear, raising the question of how fear conditioning would affect their sleep. D2 mice were implanted to record sleep via telemetry. After baseline sleep recording, groups of D2 mice were trained in cued (15 tone–shock pairings) and contextual (15 non-cued shocks) fear on 4 consecutive days. Cue and context control mice were given identical training but were never presented with shock. Sleep was recorded after shock training and after presentation of cue or context alone. Shock training produced selective suppression of REM. On the day after shock training was completed, light period sleep was significantly altered in mice in the cued fear group, but not in the contextual fear group. Subsequent presentation of fearful cues and re-exposure to the fearful contexts also produced significant reductions in REM. The effects of fear conditioning on sleep in D2 mice and other mouse strains and the differential effects of cued and contextual fear on sleep are discussed.

Effects of Transcranial Direct Current Stimulation on Consolidation of Fear Memory

It has been shown that applying transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) influences declarative memory processes. This study investigates the efficacy of tDCS on emotional memory consolidation, especially experimental fear conditioning. We applied an auditory fear-conditioning paradigm, in which two differently colored squares (blue and yellow) were presented as conditioned stimuli (CS) and an auditory stimulus as unconditioned stimulus (UCS). Sixty-nine participants were randomly assigned into three groups: anodal, cathodal, and sham stimulation. The participants of the two active groups (i.e., anodal and cathodal) received tDCS over the left DLPFC for 12 min after fear conditioning. The effect of fear conditioning and consolidation (24 h later) was measured by assessing the skin conductance response (SCR) to the CS. The results provide evidence that cathodal stimulation of the left DLPFC leads to an inhibitory effect on fear memory consolidation compared to anodal and sham stimulation, as indicated by decreased SCRs to CS+ presentation during extinction training at day 2. In conclusion, current work suggests that cathodal stimulation interferes with processes of fear memory consolidation.

Does emotion processing require attention? The effects of fear conditioning and perceptual load.

This study examined the impact of perceptual load on the processing of unattended threat-relevant faces. Participants performed a central letter-classification task while ignoring irrelevant face distractors, which appeared above or below the central task. The face distractors were graded for affective salience by means of aversive fear conditioning, with a conditioned angry face (CS+), an unconditioned angry face (CS-), and a neutral control face. The letter-classification task was presented under conditions of both low and high perceptual load. Results showed that fear conditioned (i.e., CS+) angry face distractors interfered with task performance more than CS- angry or neutral face distractors but that this interference was completely eliminated by high perceptual load. These findings demonstrate that aversively conditioned face distractors capture attention only under conditions of low perceptual load.

The effects of fear conditioning on cerebellar LTP and LTD

Long-term potentiation (LTP) and depression (LTD) at parallel fibre-Purkinje cell synapses have been described in vitro in the cerebellar cortex, but the physiological roles of these two forms of plasticity have not been well defined. Here we show that, in cerebellar slices taken from rats that had undergone fear conditioning, there was a significant occlusion of electrically induced LTP at parallel fibre-Purkinje cell synapses. This effect was long-lasting and related to associative processes, as LTP was not occluded in unpaired animals. Notably, in conditioned animals the LTP-inducing protocol produced LTD in some cells instead of LTP. Conversely, synaptic depression induced by conjunctive stimulation of parallel fibers and climbing fibres was impaired in tissue taken immediately following aversive stimulation in both paired and unpaired subjects. This effect was not, however, long-lasting as the incidence and extent of LTD returned to normal levels 24 h after behavioural testing. These findings suggest that LTP takes part in the mechanisms underlying aversive associative memories in the cerebellum.

Non-specific Effect of Fear Conditioning and Specific Effect of Social Defeat on Social Recognition Memory Performance in Female Rats

The so called “emotion learning” literature describes the ability of distressing and aversive unconditioned stimuli to classically condition a learned avoidance response. In order to investigate the impact of experience with noxious stimuli in one conditioning context on learning and memory performance in a separate, non-aversively motivated task, juvenile recognition ability was examined in adult female rats exposed previously to one of two environmental stressors. In particular, experimental adult rats were either socially defeated by exposure to an aggressive conspecific rat or fear conditioned using single or multiple pairings with footshock prior to performance of the social recognition task. Experiment 1 established that repeated exposure to a single juvenile resulted in social memory formation reflected in decreased social investigation from the first to the second exposure. Experiment 2 documented that both single and multiple pairings of an environment with footshock produced robust freezing behavior (90–95% suppression of activity). In addition, fear conditioning produced a non-specific 5–60% increase in social investigation time in both single and multiple-pairing fear conditioned groups which confounded the ability of the social recognition measure to assess effects of fear conditioning on learning and memory performance per se. In contrast, Experiment 3 documented that when social recognition memory performance was impaired to 85% of control levels by imposition of a 2 h delay, exposure to a social defeat stressor reinstated optimal social recognition memory performance. These findings suggest that the after effects of fear conditioning include non-specific alteration of social investigation whereas exposure to conspecific aggression enhances subsequent social recognition memory.

Influence of fear conditioning on elicited ponto-geniculo-occipital waves and rapid eye movement sleep.

The amygdala plays a central role in fear conditioning, a model of anticipatory anxiety. It has massive projections to brainstem regions involved in rapid eye movement sleep (REM) and ponto-geniculo-occipital (PGO) wave generation. PGO waves occur spontaneously in REM or in response to stimuli. Electrical stimulation of the central nucleus of the amygdala enhances spontaneous PGO wave activity during REM and the amplitude of both the acoustic startle response and the elicited PGO wave (PGOE), a neural marker of alerting. This study examined the effects of fear conditioning on REM and on PGOE. On conditioning days, the number of REM episodes, the average REM duration and the REM percentage were decreased while REM latency was increased. The presentation of auditory stimuli in the presence of a light conditioned stimulus produced PGOE of greater amplitudes. The results suggest that fear, most likely involving the amygdala, can influence REM and brainstem alerting mechanisms.

Effects of fear conditioning on the subsequent acquisition of an avoidance response

Four groups of rats underwent fear conditioning or control procedures prior to shuttle-box training. The four groups in the first part of the experiment received either inescapable signal-shock pairings, unpaired presentations of signal and shock, signal presentations only, or signal-shock pairings in which shock could be terminated by escape response. The result of the subsequent avoidance training demonstrated that animals which received the inescapable signal-shock pairings performed significantly better than the other three groups.

Effects of fear conditioning on subsequent avoidance behavior and movement.

Effects of fear conditioning on subsequent avoidance behavior and movement.

Effects of Fear Conditioning on Avoidance Learning

Rats were given 0, 8, 50, and 100 fear conditioning trials prior to shuttle-box avoidance learning. The fear conditioning trials resulted in: (a) an increased latency of escape responses during the initial avoidance training, (b) a greater variability of avoidance learning scores, and (c) a slight, but not statistically significant, improvement in avoidance learning. These results are attributed to fear being associated with the buzzer and to the establishing of favorable and incompatible responses to the grid shock.