scholarly journals Hippocampal-amygdala interactions mediate uncertainty-dependent resistance to extinction following fear conditioning

2019 ◽  
Author(s):  
John Morris ◽  
Francois Windels ◽  
Pankaj Sah
Keyword(s):  
Fear Conditioning ◽  
Basolateral Amygdala ◽  
Partial Reinforcement ◽  
Theta Oscillations ◽  
Field Potentials ◽  
Partial Reinforcement Extinction Effect ◽  
Reinforcement Probability ◽  
Electrophysiological Recordings ◽  
Conditioned Responding

AbstractThe partial reinforcement extinction effect (PREE) is a paradoxical learning phenomenon in which omission of reinforcement during acquisition results in more persistent conditioned responding in extinction. Here, we report a significant PREE with an inverted-U, entropy-like distribution against reinforcement probability following tone foot shock fear conditioning in rats, which was associated with increased neural activity in hippocampus and amygdala as indexed by p-ERK and c-fos immunolabelling. In vivo electrophysiological recordings of local field potentials (LFPs) showed that 50% reinforcement was associated with increases in the frequency and power of tone-evoked theta oscillations in both the subiculum region of hippocampus and in basolateral amygdala (BLA) during both acquisition (Day 1) and extinction (Day 2) sessions. Tone-evoked LFPs in 50% reinforced animals also showed increases in coherence and bidirectional Granger Causality between hippocampus and amygdala. The results support a Bayesian interpretation of the PREE, in which the phenomenon is driven by increases in the entropy or uncertainty of stimulus contingencies, and indicate a crucial role for hippocampus in mediating this uncertainty-dependent effect.

scholarly journals Hippocampus and amygdala fear memory engrams re-emerge after contextual fear reinstatement

2019 ◽  
Author(s):  
Yosif Zaki ◽  
William Mau ◽  
Christine Cincotta ◽  
Anahita Hamidi ◽  
Emily Doucette ◽  
...  
Keyword(s):  
Fear Conditioning ◽  
Basolateral Amygdala ◽  
Fear Memory ◽  
Neural Substrates ◽  
Memory Representation ◽  
Contextual Fear ◽  
Neuronal Ensembles ◽  
State Present ◽  
Insight Into

AbstractThe formation and extinction of fear memories represent two forms of learning that each engage the hippocampus and amygdala. How cell populations in these areas contribute to fear relapse, however, remains unclear. Here, we demonstrate that, in mice, cells active during fear conditioning in the dentate gyrus of hippocampus and basolateral amygdala exhibit decreased activity during extinction and are re-engaged after fear reinstatement. In vivo calcium imaging reveals that reinstatement drives population dynamics in the basolateral amygdala to revert to a network state similar to the state present during fear conditioning. Finally, we find that optogenetic inactivation of neuronal ensembles active during fear conditioning in either the hippocampus or amygdala is sufficient to disrupt fear expression after reinstatement. These results suggest that fear reinstatement triggers a partial re-emergence of the original fear memory representation, providing new insight into the neural substrates of fear relapse.

scholarly journals Fear Learning Enhances Prefrontal Cortical Suppression of Auditory Thalamic Inputs to the Amygdala in Adults, but Not Adolescents

2020 ◽  
Vol 21 (8) ◽  
pp. 3008 ◽  
Author(s):  
Nicole C. Ferrara ◽  
Eliska Mrackova ◽  
Maxine K. Loh ◽  
Mallika Padival ◽  
J. Amiel Rosenkranz
Keyword(s):  
Fear Conditioning ◽  
Behavioral Interventions ◽  
Basolateral Amygdala ◽  
Fear Learning ◽  
Memory Retention ◽  
Aversive Learning ◽  
Prefrontal Cortical ◽  
Fear And Anxiety ◽  
Stimulation Of

Adolescence is characterized by increased susceptibility to the development of fear- and anxiety-related disorders. Adolescents also show elevated fear responding and aversive learning that is resistant to behavioral interventions, which may be related to alterations in the circuitry supporting fear learning. These features are linked to ongoing adolescent development of medial prefrontal cortical (PFC) inputs to the basolateral amygdala (BLA) that regulate neural activity and contribute to the refinement of fear responses. Here, we tested the hypothesis that the extent of PFC inhibition of the BLA following fear learning is greater in adults than in adolescents, using anesthetized in vivo recordings to measure local field potentials (LFPs) evoked by stimulation of PFC or auditory thalamic (MgN) inputs to BLA. We found that BLA LFPs evoked by stimulation of MgN inputs were enhanced in adults following fear conditioning. Fear conditioning also led to reduced summation of BLA LFPs evoked in response to PFC train stimulation, and increased the capacity of PFC inhibition of MgN inputs in adults. These data suggest that fear conditioning recruits additional inhibitory capacity by PFC inputs to BLA in adults, but that this capacity is weaker in adolescents. These results provide insight into how the development of PFC inputs may relate to age differences in memory retention and persistence following aversive learning.

scholarly journals Decreased Phase–Amplitude Coupling Between the mPFC and BLA During Exploratory Behaviour in Chronic Unpredictable Mild Stress-Induced Depression Model of Rats

2021 ◽  
Vol 15 ◽  
Author(s):  
Zihe Wang ◽  
Qingying Cao ◽  
Wenwen Bai ◽  
Xuyuan Zheng ◽  
Tiaotiao Liu
Keyword(s):  
Basolateral Amygdala ◽  
Low Frequency ◽  
Exploratory Behaviour ◽  
Control Group ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Field Potentials ◽  
High Gamma ◽  
Phase Amplitude

Depression is a common neuropsychiatric illness observed worldwide, and reduced interest in exploration is one of its symptoms. The control of dysregulated medial prefrontal cortex (mPFC) over the basolateral amygdala (BLA) is related to depression. However, the oscillation interaction in the mPFC-BLA circuit has remained elusive. Therefore, this study used phase–amplitude coupling (PAC), which provides complicated forms of information transmission by the phase of low-frequency rhythm, modulating the amplitude of high-frequency rhythm, and has a potential application for the treatment of neurological disease. The chronic unpredictable mild stress (CUMS) was used to prepare the rat models of depression. Moreover, multichannel in vivo recording was applied to obtain the local field potentials (LFPs) of the mPFC, the BLA in rats in control, and CUMS groups, while they explored the open field. The results showed prominent coupling between the phase of theta oscillation (4–12 Hz) in the mPFC and the amplitude of high-gamma oscillation (70–120 Hz) in the BLA. Compared to the control group, this theta–gamma PAC was significantly decreased in the CUMS group, which was accompanied by the diminished exploratory behaviour. The results indicate that the coupling between the phase of theta in the mPFC and the amplitude of gamma in the BLA is involved in exploratory behaviour, and this decreased coupling may inhibit exploratory behaviour of rats exposed to CUMS.

scholarly journals The Partial Reinforcement Extinction Effect Depends on Learning about Non-Reinforced Trials Rather than Reinforcement Rate

2020 ◽  
Author(s):  
Justin Harris ◽  
Dorothy Kwok ◽  
Daniel Gottlieb
Keyword(s):  
Alternative Explanation ◽  
Food Pellet ◽  
Reinforcement Rate ◽  
Partial Reinforcement ◽  
The Other ◽  
Partial Reinforcement Extinction Effect ◽  
Consistent Reinforcement ◽  
Trial Probability ◽  
The Difference ◽  
Conditioned Responding

Conditioned responding extinguishes more slowly after partial (inconsistent) reinforcement than after consistent reinforcement. This Partial Reinforcement Extinction Effect (PREE) is usually attributed to learning about nonreinforcement during the partial schedule. An alternative explanation attributes it to any difference in the rate of reinforcement, arguing that animals can detect the change to nonreinforcement more quickly after a denser schedule than a leaner schedule. Experiments 1a and 1b compared extinction of magazine responding to a conditioned stimulus (CS) reinforced with one food pellet per trial and a CS reinforced with two pellets per trial. Despite the difference in reinforcement rate, there was no reliable difference in extinction. Both experiments did demonstrate the conventional PREE comparing a partial CS (50% reinforced) with a consistent CS. Experiments 2 and 3 tested whether the PREE depends specifically on learning about nonreinforced trials during partial reinforcement. Rats were trained with two CS configurations, A and AX. One was partially reinforced, the other consistently reinforced. When AX was partial and A consistent, responding to AX extinguished more slowly than to A. When AX was consistent and A was partial, there was no difference in their extinction. Therefore, pairing X with partial reinforcement allowed rats to show a PREE to AX that did not generalise to A. Pairing A with partial reinforcement meant that rats showed a PREE to A that generalised to AX. Thus, the PREE depends on learning about nonreinforced trials during partial reinforcement and is not due to any difference in per-trial probability of reinforcement

Hyperexcitability of entorhinal cortex and hippocampus after application of aminooxyacetic acid (AOAA) to layer III of the rat medial entorhinal cortex in vitro

1996 ◽  
Vol 76 (5) ◽  
pp. 2986-3001 ◽  
Author(s):  
H. E. Scharfman
Keyword(s):  
Nmda Receptor ◽  
Evoked Potentials ◽  
Entorhinal Cortex ◽  
Pyramidal Cells ◽  
Aminooxyacetic Acid ◽  
Field Potentials ◽  
Medial Entorhinal Cortex ◽  
Extracellular Recordings ◽  
Extracellular Potentials

1. Injection of aminooxyacetic acid (AOAA) into the entorhinal cortex in vivo produces acute seizures and cell loss in medial entorhinal cortex. To understand these effects, AOAA was applied directly to the medial entorhinal cortex in slices containing both the entorhinal cortex and hippocampus. Extracellular and intracellular recordings were made in both the entorhinal cortex and hippocampus to study responses to angular bundle stimulation and spontaneous activity. 2. AOAA was applied focally by leak from a micropipette or by pressure ejection. Evoked potentials increased gradually within 5 min of application, particularly the late, negative components. Evoked potentials continued to increase for up to 1 h, and these changes persisted for the remainder of the experiment (up to 5 h after drug application). 3. Paired pulse facilitation (100-ms interval) was also enhanced after AOAA application. Increasing stimulus frequency to 1-10 Hz increased evoked potentials further, and after several seconds of such stimulation multiple field potentials occurred. When stimulation was stopped at this point, repetitive field potentials occurred spontaneously for 1-2 min. These recordings, and simultaneous extracellular recordings in different layers, indicated that spontaneous synchronous activity occurred in entorhinal neurons. Intracellularly labeled cortical pyramidal cells depolarized and discharged during spontaneous and evoked field potentials. 4. The effects of AOAA were blocked reversibly by bath application of the N-methyl-D-aspartate (NMDA) receptor antagonist D-amino-5-phosphonovalerate (D-APV; 25 microM) or focal application of D-APV to the medial entorhinal cortex. 5. Simultaneous extracellular recordings from the entorhinal cortex and hippocampus demonstrated that spontaneous synchronous activity in layer III was often followed within several milliseconds by negative field potentials in the terminal zones of the perforant path (stratum moleculare of the dentate gyrus and stratum lacunosum-moleculare of area CA1). The extracellular potentials recorded in the dentate gyrus corresponded to excitatory postsynaptic potentials and action potentials in dentate granule cells. However, extracellular potentials in area CA1 were small and rarely correlated with discharge in CA1 pyramidal cells. 6. The results demonstrate that AOAA application leads to an NMDA-receptor-dependent enhancement of evoked potentials in medial entorhinal cortical neurons, which appears to be irreversible. The potentials can be facilitated by repetitive stimulation, and lead to synchronized discharges of entorhinal neurons. The discharges invade other areas such as the hippocampus, indicating how seizure activity may spread after AOAA injection in vivo. These data suggest that AOAA may be a useful tool to study longlasting changes in NMDA receptor function that lead to epileptiform activity and neurodegeneration.

scholarly journals Allopregnanolone mediates affective switching through modulation of oscillatory states in the basolateral amygdala

2021 ◽  
Author(s):  
Pantelis Antonoudiou ◽  
Phillip LW Colmers ◽  
Najah L Walton ◽  
Grant L Weiss ◽  
Anne C Smith ◽  
...  
Keyword(s):  
Basolateral Amygdala ◽  
Post Partum ◽  
Critical Role ◽  
Behavioral Outcomes ◽  
Theta Oscillations ◽  
Allosteric Modulators ◽  
Post Partum Depression ◽  
Antidepressant Effects ◽  
Behavioral States ◽  
Network States

AbstractBrexanolone (allopregnanolone), was recently approved by the FDA for the treatment of post-partum depression, demonstrating long-lasting antidepressant effects. Despite our understanding of the mechanism of action of neurosteroids as positive allosteric modulators (PAMs) of GABAa receptors, we still do not fully understand how allopregnanolone exerts these persistent antidepressant effects. Here, we demonstrate that allopregnanolone and similar synthetic neuroactive steroid analogs, SGE-516 (tool-compound) and zuranolone (SAGE-217, investigational-compound), are capable of modulating oscillatory states across species, which we propose may contribute to long-lasting changes in behavioral states. We identified a critical role for interneurons in generating oscillations in the basolateral amygdala (BLA) and a role for delta-containing GABAaRs in mediating the ability of neurosteroids to modulate network and behavioral states. Actions of allopregnanolone in the BLA is sufficient to alter behavioral states and enhance BLA high-theta oscillations (6-12Hz) through delta-containing GABAa receptors, a mechanism distinct from other GABAa PAMs, such as benzodiazepines. Moreover, treatment with the allopregnanolone analog SGE-516 induces long-lasting protection from chronic stress-induced disruption of network states, which correlates with improved behavioral outcomes. Our findings demonstrate a novel molecular and cellular mechanism mediating the well-established anxiolytic and antidepressant effects of neuroactive steroids.

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