scholarly journals Ensemble encoding of conditioned fear by prefrontal somatostatin interneurons

2021 ◽  
Author(s):  
Kirstie A Cummings ◽  
Sabina Bayshtok ◽  
Paul J Kenny ◽  
Roger L Clem
Keyword(s):  
Memory Retrieval ◽  
Conditioned Fear ◽  
Large Degree ◽  
Cell Types ◽  
Fear Learning ◽  
Gabaergic Interneurons ◽  
Memory Encoding ◽  
Neural Ensemble ◽  
Ensemble Encoding ◽  
Unique Potential

Neurons preferentially activated by learning have been ascribed the unique potential to encode memory. However, it remains unclear which genetically-defined cell types are recruited as part of such an ensemble, or what role discrete subpopulations play in behavior. Here we show that fear conditioning activates a heterogeneous neural ensemble in the medial prefrontal cortex (mPFC), comprised to a large degree of GABAergic interneurons immunoreactive for somatostatin (SST-INs). Using an intersectional genetic approach, we demonstrate that fear learning-activated SST-INs exhibit distinct circuit properties, are preferentially reactivated during memory retrieval, and mediate the expression of defensive freezing. We further show that a rewarding experience, morphine treatment, activates an orthogonal SST-IN population that exerts opposing control over fear. These results outline an important role for discrete GABAergic ensembles in fear memory encoding, and point to an unappreciated capacity for functional specialization among SST-INs.

scholarly journals Scopolamine Impairs Spatial Information Recorded With “Miniscope” Calcium Imaging in Hippocampal Place Cells

2021 ◽  
Vol 15 ◽  
Author(s):  
Dechuan Sun ◽  
Ranjith Rajasekharan Unnithan ◽  
Chris French
Keyword(s):  
Spatial Memory ◽  
Calcium Imaging ◽  
Memory Retrieval ◽  
Spatial Information ◽  
Place Cells ◽  
Network Activity ◽  
Memory Encoding ◽  
Neural Firing ◽  
Neural Ensemble ◽  
Hippocampal Network

The hippocampus and associated cholinergic inputs have important roles in spatial memory in rodents. Muscarinic acetylcholine receptors (mAChRs) are involved in the communication of cholinergic signals and regulate spatial memory. They have been found to impact the memory encoding process, but the effect on memory retrieval is controversial. Previous studies report that scopolamine (a non-selective antagonist of mAChR) induces cognitive deficits on animals, resulting in impaired memory encoding, but the effect on memory retrieval is less certain. We tested the effects of blocking mAChRs on hippocampal network activity and neural ensembles that had previously encoded spatial information. The activity of hundreds of neurons in mouse hippocampal CA1 was recorded using calcium imaging with a miniaturised fluorescent microscope and properties of place cells and neuronal ensemble behaviour in a linear track environment were observed. We found that the decoding accuracy and the stability of spatial representation revealed by hippocampal neural ensemble were significantly reduced after the administration of scopolamine. Several other parameters, including neural firing rate, total number of active neurons, place cell number and spatial information content were affected. Similar results were also observed in a simulated hippocampal network model. This study enhances the understanding of the function of mAChRs on spatial memory impairment.

scholarly journals Linking the Rapid Cascade of Visuo-Attentional Processes to Successful Memory Encoding

2020 ◽  
Author(s):  
B R Geib ◽  
R Cabeza ◽  
M G Woldorff
Keyword(s):  
Visual Processing ◽  
Memory Retrieval ◽  
Current Knowledge ◽  
High Temporal Resolution ◽  
Alpha Power ◽  
Attentional Orienting ◽  
Memory Encoding ◽  
Attentional Processes ◽  
Neural Processes ◽  
Dm Effect

Abstract While it is broadly accepted that attention modulates memory, the contribution of specific rapid attentional processes to successful encoding is largely unknown. To investigate this issue, we leveraged the high temporal resolution of electroencephalographic recordings to directly link a cascade of visuo-attentional neural processes to successful encoding: namely (1) the N2pc (peaking ~200 ms), which reflects stimulus-specific attentional orienting and allocation, (2) the sustained posterior-contralateral negativity (post-N2pc), which has been associated with sustained visual processing, (3) the contralateral reduction in oscillatory alpha power (contralateral reduction in alpha > 200 ms), which has also been independently related to attentionally sustained visual processing. Each of these visuo-attentional processes was robustly predictive of successful encoding, and, moreover, each enhanced memory independently of the classic, longer-latency, conceptually related, difference-due-to memory (Dm) effect. Early latency midfrontal theta power also promoted successful encoding, with at least part of this influence being mediated by the later latency Dm effect. These findings markedly expand current knowledge by helping to elucidate the intimate relationship between attentional modulations of perceptual processing and effective encoding for later memory retrieval.

scholarly journals Observational Fear Learning in Rats: Role of Trait Anxiety and Ultrasonic Vocalization

2021 ◽  
Vol 11 (4) ◽  
pp. 423
Author(s):  
Markus Fendt ◽  
Claudia Paulina Gonzalez-Guerrero ◽  
Evelyn Kahl
Keyword(s):  
Trait Anxiety ◽  
Conditioned Fear ◽  
Ultrasonic Vocalization ◽  
Fear Learning ◽  
Anxiety State ◽  
Learning Procedure ◽  
The Social ◽  
Medium Level ◽  
Male Wistar Rats

Rats can acquire fear by observing conspecifics that express fear in the presence of conditioned fear stimuli. This process is called observational fear learning and is based on the social transmission of the demonstrator rat’s emotion and the induction of an empathy-like or anxiety state in the observer. The aim of the present study was to investigate the role of trait anxiety and ultrasonic vocalization in observational fear learning. Two experiments with male Wistar rats were performed. In the first experiment, trait anxiety was assessed in a light–dark box test before the rats were submitted to the observational fear learning procedure. In the second experiment, ultrasonic vocalization was recorded throughout the whole observational fear learning procedure, and 22 kHz and 50 kHz calls were analyzed. The results of our study show that trait anxiety differently affects direct fear learning and observational fear learning. Direct fear learning was more pronounced with higher trait anxiety, while observational fear learning was the best with a medium-level of trait anxiety. There were no indications in the present study that ultrasonic vocalization, especially emission of 22 kHz calls, but also 50 kHz calls, are critical for observational fear learning.

scholarly journals Fear conditioning and stimulus generalization in association with age in children and adolescents

2021 ◽  
Author(s):  
Julia Reinhard ◽  
Anna Slyschak ◽  
Miriam A. Schiele ◽  
Marta Andreatta ◽  
Katharina Kneer ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Fear Conditioning ◽  
Repeated Measures ◽  
Conditioned Fear ◽  
Fear Learning ◽  
Stimulus Generalization ◽  
Healthy Children ◽  
Older Individuals ◽  
Age Related ◽  
Current Task

AbstractThe aim of the study was to investigate age-related differences in fear learning and generalization in healthy children and adolescents (n = 133), aged 8–17 years, using an aversive discriminative fear conditioning and generalization paradigm adapted from Lau et al. (2008). In the current task, participants underwent 24 trials of discriminative conditioning of two female faces with neutral facial expressions, with (CS+) or without (CS−) a 95-dB loud female scream, presented simultaneously with a fearful facial expression (US). The discriminative conditioning was followed by 72 generalization trials (12 CS+, 12 GS1, 12 GS2, 12 GS3, 12 GS4, and 12 CS−): four generalization stimuli depicting gradual morphs from CS+ to CS− in 20%-steps were created for the generalization phases. We hypothesized that generalization in children and adolescents is negatively correlated with age. The subjective ratings of valence, arousal, and US expectancy (the probability of an aversive noise following each stimulus), as well as skin conductance responses (SCRs) were measured. Repeated-measures ANOVAs on ratings and SCR amplitudes were calculated with the within-subject factors stimulus type (CS+, CS−, GS1-4) and phase (Pre-Acquisition, Acquisition 1, Acquisition 2, Generalization 1, Generalization 2). To analyze the modulatory role of age, we additionally calculated ANCOVAs considering age as covariate. Results indicated that (1) subjective and physiological responses were generally lower with increasing age irrespective to the stimulus quality, and (2) stimulus discrimination improved with increasing age paralleled by reduced overgeneralization in older individuals. Longitudinal follow-up studies are required to analyze fear generalization with regard to brain maturational aspects and clarify whether overgeneralization of conditioned fear promotes the development of anxiety disorders or vice versa.

scholarly journals Npas4a expression in the teleost forebrain is associated with stress coping style differences in fear learning

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Matthew R. Baker ◽  
Ryan Y. Wong
Keyword(s):  
Neural Plasticity ◽  
Coping Style ◽  
Molecular Mechanisms ◽  
Conditioned Fear ◽  
Coping Styles ◽  
Brain Regions ◽  
Contextual Fear Conditioning ◽  
Fear Learning ◽  
Stress Coping ◽  
Contextual Fear

AbstractLearning to anticipate potentially dangerous contexts is an adaptive behavioral response to coping with stressors. An animal’s stress coping style (e.g. proactive–reactive axis) is known to influence how it encodes salient events. However, the neural and molecular mechanisms underlying these stress coping style differences in learning are unknown. Further, while a number of neuroplasticity-related genes have been associated with alternative stress coping styles, it is unclear if these genes may bias the development of conditioned behavioral responses to stressful stimuli, and if so, which brain regions are involved. Here, we trained adult zebrafish to associate a naturally aversive olfactory cue with a given context. Next, we investigated if expression of two neural plasticity and neurotransmission-related genes (npas4a and gabbr1a) were associated with the contextual fear conditioning differences between proactive and reactive stress coping styles. Reactive zebrafish developed a stronger conditioned fear response and showed significantly higher npas4a expression in the medial and lateral zones of the dorsal telencephalon (Dm, Dl), and the supracommissural nucleus of the ventral telencephalon (Vs). Our findings suggest that the expression of activity-dependent genes like npas4a may be differentially expressed across several interconnected forebrain regions in response to fearful stimuli and promote biases in fear learning among different stress coping styles.

scholarly journals Conditioned fear reactions are associated with gray matter density but not cortical microstructure

2020 ◽  
Author(s):  
Christoph Fraenz ◽  
Dorothea Metzen ◽  
Christian J. Merz ◽  
Helene Selpien ◽  
Nikolai Axmacher ◽  
...  
Keyword(s):  
Gray Matter ◽  
Conditioned Fear ◽  
Brain Networks ◽  
Brain Regions ◽  
Matter Density ◽  
Fear Learning ◽  
Future Research ◽  
Fear Reaction ◽  
Gray Matter Density ◽  
Diffusion Weighted Images

AbstractResearch has shown that fear acquisition, in reaction to potentially harmful stimuli or situations, is characterized by pronounced interindividual differences. It is likely that such differences are evoked by variability in the macro- and microstructural properties of brain regions involved in the processing of threat or safety signals from the environment. Indeed, previous studies have shown that the strength of conditioned fear reactions is associated with the cortical thickness or volume of various brain regions. However, respective studies were exclusively targeted at single brain regions instead of whole brain networks. Here, we tested 60 young and healthy individuals in a differential fear conditioning paradigm while they underwent fMRI scanning. In addition, we acquired T1-weighted and multi-shell diffusion-weighted images prior to testing. We used task-based fMRI data to define global brain networks which exhibited increased BOLD responses towards CS+ or CS- presentations, respectively. From these networks, we obtained mean values of gray matter density, neurite density, and neurite orientation dispersion. We found that mean gray matter density averaged across the CS+ network was significantly correlated with the strength of conditioned fear reactions quantified via skin conductance response. Measures of neurite architecture were not associated with conditioned fear reaction in any of the two networks. Our results extend previous findings on the relationship between brain morphometry and fear learning. Most importantly, our study is the first to introduce neurite imaging to fear learning research and discusses how its implementation can be improved in future research.

Physiological Properties of Central Medial and Central Lateral Amygdala Neurons

1999 ◽  
Vol 82 (4) ◽  
pp. 1843-1854 ◽  
Author(s):  
Marzia Martina ◽  
Sébastien Royer ◽  
Denis Paré
Keyword(s):  
Conditioned Fear ◽  
Brain Slices ◽  
Cell Types ◽  
Membrane Depolarization ◽  
Membrane Properties ◽  
Repetitive Firing ◽  
Inward Rectification ◽  
Current Pulses ◽  
Outward Rectification ◽  
Physiological Properties

Mounting evidence implicates the central (CE) nucleus of the amygdala in the mediation of classically conditioned fear responses. However, little data are available regarding the intrinsic membrane properties of CE amygdala neurons. Here, we characterized the physiological properties of CE medial (CEM) and CE lateral (CEL) amygdala neurons using whole cell recordings in brain slices maintained in vitro. Several classes of CE neurons were distinguished on the basis of their physiological properties. Most CEM cells (95%), here termed “late-firing neurons,” displayed a marked voltage- and time-dependent outward rectification in the depolarizing direction. This phenomenon was associated with a conspicuous delay between the onset of depolarizing current pulses and the first action potential. During this delay, the membrane potential ( V m) depolarized slowly, the steepness of this depolarizing ramp increasing as the prepulse V m was hyperpolarized from −60 to −90 mV. Low extracellular concentrations of 4-aminopyridine (30 μM) reversibly abolished the outward rectification and the delay to firing. Late-firing CEM neurons displayed a continuum of repetitive firing properties with cells generating single spikes at one pole and high-frequency (≥90 Hz) spike bursts at the other. In contrast, only 56% of CEL cells displayed the late-firing behavior prevalent among CEM neurons. Moreover, these CEL neurons only generated single spikes in response to membrane depolarization. A second major class of CEL cells (38%) lacked the characteristic delay to firing observed in CEM cells, generated single spikes in response to membrane depolarization, and displayed various degrees of inward rectification in the hyperpolarizing direction. In both regions of the CE nucleus, two additional cell types were encountered infrequently (≤ 6% of our samples). One type of neurons, termed “low-threshold bursting cells” had a behavior reminiscent of thalamocortical neurons. The second type of cells, called “fast-spiking cells,” generated brief action potentials at high rates with little spike frequency adaptation in response to depolarizing current pulses. These findings indicate that the CE nucleus contains several types of neurons endowed with distinct physiological properties. Moreover, these various cell types are not distributed uniformly in the medial and lateral sector of the CE nucleus. This heterogeneity parallels anatomic data indicating that these subnuclei are part of different circuits.

Acquisition of Fear and Extinction in Lateral Amygdala: A Modeling Study

2010 ◽  
Author(s):  
Sandeep Pendyam ◽  
Dongbeom Kim ◽  
Gregory J. Quirk ◽  
Satish S. Nair
Keyword(s):  
Pyramidal Neurons ◽  
Conditioned Fear ◽  
Fear Memory ◽  
Fear Learning ◽  
Cell Populations ◽  
Storage Site ◽  
Somatosensory Information ◽  
Cortical Inputs ◽  
Lateral Nucleus ◽  
And Storage

The lateral nucleus of amygdala (LA) is known to be a critical storage site for conditioned fear memory. Synaptic plasticity at auditory inputs to the dorsal LA (LAd) is critical for the formation and storage of auditory fear memories. Recent evidence suggests that two different cell populations (transient- and long-term plastic cells) are present in LAd and are responsible for fear learning. However, the mechanisms involved in the formation and storage of fear are not well understood. As an extension of previous work, a biologically realistic computational model of the LAd circuitry is developed to investigate these mechanisms. The network model consists of 52 LA pyramidal neurons and 13 interneurons. Auditory and somatosensory information reaches LA from both thalamic and cortical inputs. The model replicated the tone responses observed in the two LAd cell populations during conditioning and extinction. The model provides insights into the role of thalamic and cortical inputs in fear memory formation and storage.

F10. Cue-Induced Conditioned Fear Learning Requires Orexin Receptor 1 Signaling in the Central Amygdala

2019 ◽  
Vol 85 (10) ◽  
pp. S216-S217
Author(s):  
Erik Dustrude ◽  
Izabela Caliman ◽  
Cristian Bernabe ◽  
Stephanie Fitz ◽  
Laura Grafe ◽  
...  
Keyword(s):  
Conditioned Fear ◽  
Fear Learning ◽  
Central Amygdala

Anterior Hippocampus Orchestrates Successful Encoding and Retrieval of Non-relational Memory: An Event-related FMRI Study

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
T. Kircher
Keyword(s):  
Memory Retrieval ◽  
Parahippocampal Gyrus ◽  
Elderly Subjects ◽  
Relational Memory ◽  
Memory Encoding ◽  
Ageing Society ◽  
Healthy Elderly ◽  
Left Hippocampus ◽  
Healthy Elderly Subjects ◽  
Encoding And Retrieval

Episodic memory encoding and retrieva processes have been linked to different neural networks. However, the common brain regions associated with non-relational memory processing during successful encoding (subsequent memory effect) and successful retrieval (recognition effect) have not yet been investigated. Further, the majority of functional imaging studies have been conducted in young subjects, whereas patients from lesion studies, where most neuropsychological models are still based upon, are usually older. Inferences from younger subjects cannot necessarily be applied to the elderly, an issue becoming particularly relevant with our ageing society. Using an event-related fMRI approach we studied 29 healthy elderly subjects (mean age 67.8, SD 5.4 years) with a non-associative task of intentional word list encoding and retrieval. For each subject, behavioural responses were individually classified into four event types (hits, misses, false alarms, correct rejections). Brain areas activated during successful memory encoding comprised the anterior left hippocampus extending into the surrounding parahippocampal gyrus. Regions associated with successful memory retrieval involved a widespread network of anterior left parahippocampal gyrus, bilateral temporal cortices and bilateral ventral and dorsal prefrontal areas. Regions contributing to both successful encoding and retrieval, evidenced by a conjunction analysis, revealed prominent left lateralized activations of the anterior hippocampus and the inferior parietal lobe. Our results indicate that the anterior left hippocampus plays an important role during successful memory encoding and during successful memory retrieval in a task of simple, non-associative wordlist learning in healthy elderly subjects.

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