scholarly journals Prefrontal somatostatin interneurons encode fear memory

2019 ◽  
Author(s):  
Kirstie A. Cummings ◽  
Roger L. Clem
Keyword(s):  
Specific Activity ◽  
Conditioned Fear ◽  
Gain Control ◽  
Brain Regions ◽  
Fear Learning ◽  
Causal Mechanism ◽  
Projection Neurons ◽  
Synaptic Organization ◽  
Cortical Projection ◽  
Output Neurons

AbstractTheories stipulate that memories are encoded within networks of cortical projection neurons (PNs). Conversely, GABAergic interneurons (INs) are thought to function primarily to inhibit PNs and thereby impose network gain control, an important but purely modulatory role. However, we found that associative fear learning potentiates synaptic transmission and cue-specific activity of medial prefrontal cortex (mPFC) somatostatin interneurons (SST-INs), and that activation of these cells controls both memory encoding and expression. Furthermore, the synaptic organization of SST- and parvalbumin (PV)-INs provides a potential circuit basis for SST-IN-evoked disinhibition of mPFC output neurons and recruitment of remote brain regions associated with defensive behavior. These data suggest that rather than constrain mnemonic processing, potentiation of SST-IN activity represents an important causal mechanism for conditioned fear.

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.

Distribution of terminals from pedunculopontine tegmental nucleus and synaptic organization in lateralis medialis-suprageniculate nucleus of cat's thalamus: Anterograde tracing, immunohistochemical studies, and quantitative analysis

2000 ◽  
Vol 17 (6) ◽  
pp. 893-904 ◽  
Author(s):  
KAEKO HOSHINO ◽  
YOSHIMITSU Y. KATOH ◽  
WANZHU BAI ◽  
TADAYOSHI KAIYA ◽  
MASAO NORITA
Keyword(s):  
Brain Regions ◽  
Pedunculopontine Tegmental Nucleus ◽  
Association Cortex ◽  
Projection Neurons ◽  
Synaptic Organization ◽  
Electron Microscopic ◽  
Synaptic Contacts ◽  
Tegmental Nucleus ◽  
Visual Association Cortex ◽  
Immunohistochemical Studies

The cat's lateralis medialis-suprageniculate nuclear complex (LM-Sg) in the thalamus receives input from various brain regions such as the superior colliculus, brain stem, and spinal cord, as well as from visual association cortex. In a previous study, we demonstrated that LM-Sg receives cholinergic fibers from the pedunculopontine tegmental nucleus (PPT) and that cholinergic terminals make synaptic contacts with the dendrites of glutamatergic projection neurons and of GABAergic interneurons (Hoshino et al., 1997). In this study, we investigate the distribution and the organization of PPT terminals by means of a combined anterograde tracer (biotinylated dextran amine, BDA) and immunohistochemical methods. When stained by acetylcholinesterase (AChE), the LM-Sg is not uniformly immunoreactive, but rather is patchily labeled and shows a streaming type of reactivity. The tissue content appears high in enzyme activity in AChE-positive zones and is much lighter in activity in AChE-negative zones. We compared the synaptic organization between AChE-positive and AChE-negative portions of the LM-Sg in separate groups of electron-microscopic material: four types of vesicle containing profiles (RS, RL, F1, and PSD) as well as synaptic glomeruli were observed in this nucleus. Among these, the PSD profiles were observed more frequently in AChE-positive portions than in AChE-negative zones. Furthermore, the number of glomeruli was significantly higher in AChE-positive than in AChE-negative zones. Following the injection of BDA into PPT, labeled terminals within LM-Sg were rather more concentrated in the AChE-positive portion. Although the majority of PPT terminals made synaptic contacts with dendrites in the neuropil, a few terminals were involved in the synaptic glomeruli. The present results show that the synaptic organization is distinctly different between the AChE-positive and AChE-negative portions of LM-Sg. These results suggest that the AChE-positive portions of LM-Sg are relatively more involved in integrating information arising from a diverse set of inputs and processing that information within glomeruli in a complex manner than occurs in the AChE-negative portion of LM-Sg.

scholarly journals Long-range interhemispheric projection neurons show biased response properties and fine-scale local subnetworks in mouse visual cortex

2019 ◽  
Author(s):  
Kenta M. Hagihara ◽  
Ayako W. Ishikawa ◽  
Yumiko Yoshimura ◽  
Yoshiaki Tagawa ◽  
Kenichi Ohki
Keyword(s):  
Long Range ◽  
Brain Regions ◽  
Projection Neurons ◽  
Fine Scale ◽  
Local Connectivity ◽  
Cortical Projection ◽  
Response Properties ◽  
Brain Functions ◽  
Mouse Visual Cortex

SummaryIntegration of information processed separately in distributed brain regions is essential for brain functions. This integration is enabled by long-range projection neurons, and further, concerted interactions between long-range projections and local microcircuits are crucial. It is not well known, however, how this interaction is implemented in cortical circuits. Here, to decipher this logic, using callosal projection neurons (CPNs) as a model of long-range projections, we found that CPNs exhibited distinct response properties and fine-scale local connectivity patterns. In vivo 2-photon calcium imaging revealed that CPNs showed a higher ipsilateral eye (with respect to their somata) preference, and that CPN pairs showed stronger signal/noise correlation than random pairs. Slice recordings showed CPNs were preferentially connected to CPNs, demonstrating the existence of projection target-dependent fine-scale subnetworks. Collectively, our results suggest that long-range projection target predicts response properties and local connectivity of cortical projection neurons.

scholarly journals Scn1a-GFP transgenic mouse revealed Nav1.1 expression in neocortical pyramidal tract projection neurons

2021 ◽  
Author(s):  
Tetsushi Yamagata ◽  
Ikuo Ogiwara ◽  
Tetsuya Tatsukawa ◽  
Yuka Otsuka ◽  
Emi Mazaki ◽  
...  
Keyword(s):  
Transgenic Mouse ◽  
Fluorescent Protein ◽  
Pyramidal Tract ◽  
Brain Regions ◽  
Dravet Syndrome ◽  
Inhibitory Neurons ◽  
Projection Neurons ◽  
Cortical Projection ◽  
Distinct Subpopulation ◽  
Excitatory Neurons

AbstractExpressions of voltage-gated sodium channels Nav1.1 and Nav1.2, encoded by SCN1A and SCN2A genes, respectively, have been reported to be mutually exclusive in most brain regions. In adult neocortex, Nav1.1 is dominant in inhibitory neurons while Nav1.2 is dominant in excitatory neurons. Although a distinct subpopulation of neocortical excitatory neurons was also reported to express Nav1.1, their nature has been uncharacterized. By using newly-generated transgenic mouse lines expressing Scn1a promoter-driven green fluorescent protein (GFP), here we confirm mutually-exclusive expressions of Nav1.1 and Nav1.2, absence of Nav1.1 in hippocampal excitatory neurons, and further show that among neocortical excitatory neurons Nav1.1 is expressed in pyramidal tract and a subpopulation of cortico-cortical while Nav1.2 in cortico-striatal, cortico-thalamic and a distinct subpopulation of cortico-cortical projection neurons. These observations now contribute to the elucidation of pathological neural circuits for epilepsies and neurodevelopmental disorders caused by SCN1A and SCN2A mutations including sudden death in Dravet syndrome.

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

2020 ◽  
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 magnitude of 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.

Computational Modeling of Lateral Amygdala Neurons During Acquisition and Extinction of Conditioned Fear, Using Hebbian Learning

2006 ◽  
Author(s):  
Guoshi Li ◽  
Stacy Cheng ◽  
Frank Ko ◽  
Scott L. Raunch ◽  
Gregory Quirk ◽  
...  
Keyword(s):  
Medial Temporal Lobe ◽  
Hebbian Learning ◽  
Conditioned Fear ◽  
Fear Learning ◽  
Central Nucleus ◽  
Projection Neurons ◽  
Basal Nucleus ◽  
Learned Fear ◽  
Main Components ◽  
Lateral Nucleus

The amygdaloid complex located within the medial temporal lobe plays an important role in the acquisition and expression of learned fear associations (Quirk et al. 2003) and contains three main components: the lateral nucleus (LA), the basal nucleus (BLA), and the central nucleus (CE) (Faber and Sah, 2002). The lateral nucleus of the amygdala (LA) is widely accepted to be a key site of plastic synaptic events that contributes to fear learning (Pare, Quirk, LeDoux, 2004). There are two main types of neurons within the LA and the BLA: principal pyramidal-like cells which form projection neurons and are glutamatergic and local circuit GABAergic interneurons (Faber and Sah, 2002). In auditory fear conditioning, convergence of tone [conditioned stimulus (CS)] and foot-shock [unconditioned stimulus (US)] inputs potentiates the synaptic transmission containing CS information from the thalamus and cortex to LA, which leads to larger responses in LA in the presentation of subsequent tones only. The increasing LA responses disinhibit the CE neurons via the intercalated (ITC) cells, eliciting fear responses via excessive projections to brain stem and hypothalamic sites (Pare, Quirk, LeDoux, 2004). As a result, rats learn to freeze to a tone that predicts a foot-shock. Once acquired, conditioned fear associations are not always expressed and repeated presentation of the tone CS in the absence of US causes conditioned fear responses to rapidly diminish, a phenomenon termed fear extinction (Quirk et al. 2003). Extinction does not erase the CS-US association, instead it forms a new memory that inhibits conditioned response (Quirk et al. 2003)

scholarly journals Biased connectivity of brain-wide inputs to ventral subiculum output neurons

2019 ◽  
Author(s):  
RWS Wee ◽  
AF MacAskill
Keyword(s):  
Spatial Location ◽  
Brain Regions ◽  
Afferent Input ◽  
Projection Neurons ◽  
Nucleus Reuniens ◽  
Downstream Target ◽  
Ventral Subiculum ◽  
Mouse Hippocampus ◽  
Output Neurons ◽  
Relationship Of

AbstractThe ventral subiculum (vS) of the mouse hippocampus coordinates diverse behaviours through heterogeneous populations of projection neurons. These neurons transmit signals to multiple brain regions by integrating thousands of local and long-range synaptic inputs. However, whether each population is selectively innervated by different afferent input remains unknown. To address this question, we employed projection-specific rabies tracing to study the input-output relationship of vS output neurons. Analysis of brain-wide inputs reveals quantitative input differences that can be explained by the spatial location of postsynaptic neurons along the proximal-distal axis of vS and the identity of the downstream target. Further, the input from nucleus reuniens, an area thought to underlie vS and prefrontal cortex (PFC) reciprocal connectivity, is unexpectedly biased away from PFC-projecting vS neurons. Overall, we reveal prominent heterogeneity in brain-wide inputs to the vS parallel output circuitry, providing a basis for the selective control of individual projections during behaviour.

scholarly journals Serotonergic regulation of corticoamygdalar neurons in the mouse prelimbic cortex

2018 ◽  
Author(s):  
Daniel Avesar ◽  
Emily K. Stephens ◽  
Allan T. Gulledge
Keyword(s):  
Pyramidal Neurons ◽  
Conditioned Fear ◽  
Morphological Characteristics ◽  
Morphological Characterization ◽  
Projection Neurons ◽  
Prelimbic Cortex ◽  
Cortical Projection ◽  
Dual Tracer ◽  
Biphasic Responses

AbstractNeuromodulatory transmitters, such as serotonin (5-HT), selectively regulate the excitability of subpopulations of cortical projection neurons to gate cortical output to specific target regions. For instance, in the mouse prelimbic cortex, 5-HT selectively excites commissurally projecting intratelencephalic (COM) neurons via activation of 5-HT2A (2A) receptors, while simultaneously inhibiting corticofugally projecting pyramidal neurons targeting the pons via 5-HT1A (1A) receptors. Here we characterize the physiology, morphology, and serotonergic regulation of corticoamygdalar (CAm) projection neurons in the mouse prelimbic cortex. Layer 5 CAm neurons shared a number of physiological and morphological characteristics with COM neurons, including higher input resistances, smaller HCN-channel mediated responses, and sparser dendritic arbors than corticopontine neurons. Across cortical lamina, CAm neurons also resembled COM neurons in their serotonergic modulation; focally applied 5-HT (100 µM; 1 s) generated 2A-receptor-mediated excitation, or 1A- and 2A- dependent biphasic responses, in ipsilaterally and contralaterally projecting CAm neurons. Serotonergic excitation depended on extrinsic excitatory drive, as 5-HT failed to depolarize CAm neurons from rest, but could enhance the number of action potentials generated by simulated barrages of synaptic input. Finally, using dual tracer injections, we identified double-labeled CAm/COM neurons that displayed primarily excitatory or biphasic responses to 5-HT. Overall, our findings reveal that prelimbic CAm neurons overlap with COM neurons, and that both neuron subtypes exhibit 2A-dependent serotonergic excitation. Our findings suggest that 5-HT, acting at 2A receptors, will promote cortical output to the amygdala.Significance StatementCortical projections to the amygdala allow for executive “top-down” control of emotional responses. Corticoamygdalar (CAm) neurons in the prelimbic cortex contribute to the learning and expression of conditioned fear responses, processes that may also be regulated by serotonin (5-HT). Our study provides a physiological and morphological characterization of prelimbic CAm neurons, and demonstrates that the excitability of CAm neurons is regulated by 5-HT acting at 5-HT2A receptors alone, or in combination with 5-HT1A receptors. Our results suggest that 5-HT may regulate corticoamygdalar circuits during the learning and expression of conditioned fear.

Recalling Safety: Cooperative Functions of the Ventromedial Prefrontal Cortex and the Hippocampus in Extinction

CNS Spectrums ◽  
2007 ◽  
Vol 12 (3) ◽  
pp. 200-206 ◽  
Author(s):  
Kevin A. Corcoran ◽  
Gregory J. Quirk
Keyword(s):  
Prefrontal Cortex ◽  
Neural Plasticity ◽  
Neural Circuit ◽  
Contextual Information ◽  
Conditioned Fear ◽  
Brain Regions ◽  
Ventromedial Prefrontal Cortex ◽  
Fear Learning ◽  
Extinction Learning ◽  
Fear And Anxiety

ABSTRACTAnxiety disorders are commonly treated with exposure-based therapies that rely on extinction of conditioned fear. Persistent fear and anxiety following exposure therapy could reflect a deficit in the recall of extinction learning. Animal models of fear learning have elucidated a neural circuit for extinction learning and recall that includes the amygdala, ventromedial prefrontal cortex (vmPFC), and hippocampus. Whereas the amygdala is important for extinction learning, the vmPFC is a site of neural plasticity that allows for the inhibition of fear during extinction recall. We suggest that the vmPFC receives convergent information from other brain regions, such as contextual information from the hippocampus, to determine the circumstances under which extinction or fear will be recalled. Imaging studies of human fear conditioning and extinction lend credence to this extinction network. Understanding the neural circuitry underlying extinction recall will lead to more effective therapies for disorders of fear and anxiety.

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