Activity of the anterior cingulate cortex and ventral hippocampus underlie increases in contextual fear generalization

Cullen, Patrick K.; Gilman, T. Lee; Winiecki, Patrick; Riccio, David C.; Jasnow, Aaron M.

doi:10.1016/j.nlm.2015.07.001

Cited by 92 publications

(140 citation statements)

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“…Despite the importance of fear generalization as a fundamental component underlying many anxiety disorders (Brewin, 2001;Grillon and Morgan, 1999;Jovanovic et al, 2009), we do not fully understand how this phenomenon occurs. However, some recent evidence from our laboratory has uncovered specific brain regions (Cullen et al, 2015) and neural mechanisms underlying generalization (Cullen et al, 2014), and this evidence implicates a critical role for the GABAergic system.…”

Section: Introductionmentioning

confidence: 89%

“…A single guide cannula (Plastics One, Inc) was inserted into the skull above the lateral ventricle at the GABAB(1a) receptors and fear generalization JF Lynch et al following coordinates with respect to bregma (−2.10 mm D/V, − 0.34 mm A/P, +1 mm M/L) including a 1 mm protrusion for the infusion needle. Cannulations into specific brain regions were completed as described previously (Cullen et al, 2015). Briefly, for insertion into the dorsal CA1, bilateral guide cannulae were surgically implanted using a 14°angle (−1.6 mm D/V, − 2.5 mmA/P, +2.5 mm M/L) with a 1 mm infusion needle.…”

Section: Surgical Proceduresmentioning

confidence: 99%

“…When infusions were directed towards the dorsal CA1 before context memory retrieval, vehicle-treated, (t(23) = 2.94, po0.01), and drug-treated animals displayed significant memory precision, (t(14) = 3.22, po0.01) (Figure 4e), indicating little generalized fear. We previously demonstrated that activity of the ventral CA1 of the hippocampus and the ACC were critically involved in time-dependent contextual fear generalization (Cullen et al, 2015). Inactivation of the ventral CA1 or the ACC during a remote retrieval test (21 days after training) attenuated generalized contextual fear (Cullen et al, 2015).…”

Section: Hippocampal Gaba B(1a) Receptors Constrain Contextual Fear Gmentioning

confidence: 99%

“…For example, Arc mRNA activity increases in the anterior cingulate cortex (ACC) and ventral hippocampus during expression of a generalized fear, implicating activity of these structures in contextual fear generalization. Inactivation of the ACC or ventral hippocampus before retrieval at a long retention interval significantly attenuates generalized contextual fear (Cullen et al, 2015). GABA B(1a) receptors are located at glutamatergic terminals in neocortical and hippocampal pyramidal neurons (Jacobson et al, 2007b;Shaban et al, 2006;Vigot et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

“…GABA B(1a) receptors are located at glutamatergic terminals in neocortical and hippocampal pyramidal neurons (Jacobson et al, 2007b;Shaban et al, 2006;Vigot et al, 2006). Given the involvement of these structures both in processing contextual information (Bannerman et al, 2002;Bannerman et al, 1999;Kjelstrup et al, 2002;Moser et al, 1993;Moser and Moser, 1998), and in fear generalization (Cullen et al, 2014;Cullen et al, 2015), the current study was designed to explore when presynaptic GABA B(1a) receptors contribute to contextual discrimination, thereby constraining generalized fear. In order to assess this, C57BL/6 male mice received cannula implants aimed at the lateral ventricle and were infused with a GABA B(1a) receptor-specific antagonist CGP 36216.…”

Section: Introductionmentioning

confidence: 99%

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Hippocampal GABAB(1a) Receptors Constrain Generalized Contextual Fear

Lynch

Winiecki

Gilman

et al. 2016

Neuropsychopharmacol

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Many anxiety disorders are characterized by generalization of fear responses to neutral or ambiguous stimuli. Therefore, a comprehensive understanding of the mechanisms contributing to generalized fear is essential for formulating successful treatments for anxiety disorders. Previous research shows that GABA-mediated presynaptic inhibition has a critical role in cued fear generalization, as animals with genetically deleted presynaptic GABA B(1a) receptors cannot discriminate between CS+ and CS − tones. Work from our laboratory has further identified that GABA B(1a) receptors are necessary for maintaining contextual memory precision, thereby constraining generalized contextual fear. We previously found that GABA B(1a) KO mice show generalized fear to a neutral context 24 h after training, but not 2 h after training. A similar pattern was observed with object location and recognition, suggesting that this receptor subtype affects consolidation and/or retrieval of precise contextual and spatial memories. Here we sought to specifically examine the involvement of GABA B(1a) receptors in consolidation or retrieval of a precise fear memory. To do so, we infused a selective GABA B(1a) receptor antagonist, CGP 36216, intracerebroventricularly (ICV), or locally into the dorsal hippocampus, ventral hippocampus, or anterior cingulate cortex (ACC), during consolidation and retrieval of context fear training. Blockade of GABA B(1a) receptors through ICV, dorsal hippocampal, or ventral hippocampal infusions 'after' training (consolidation) resulted in fear generalization to the neutral context when mice were tested 24, but not 6 h after training. Post-training infusions of CGP into the ACC, however, did not promote generalized fear. In addition, ICV, dorsal hippocampal, ventral hippocampal, or ACC infusions immediately 'before' testing (retrieval) did not result in context fear generalization. These data suggest that GABA-mediated presynaptic inhibition is not critical for retrieval of precise contextual memory, but rather has an important role in the long-term consolidation of precise contextual memories and constrains generalized fear responses.

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Section: Introductionmentioning

confidence: 89%

Section: Surgical Proceduresmentioning

confidence: 99%

Section: Hippocampal Gaba B(1a) Receptors Constrain Contextual Fear Gmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Hippocampal GABAB(1a) Receptors Constrain Generalized Contextual Fear

Lynch

Winiecki

Gilman

et al. 2016

Neuropsychopharmacol

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Significance of the anterior cingulate cortex in neurogenesis plasticity: Connections, functions, and disorders across postnatal and adult stages

Naffaa

2023

BioEssays

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The anterior cingulate cortex (ACC) is a complex and continually evolving brain region that remains a primary focus of research due to its multifaceted functions. Various studies and analyses have significantly advanced our understanding of how the ACC participates in a wide spectrum of memory and cognitive processes. However, despite its strong connections to brain areas associated with hippocampal and olfactory neurogenesis, the functions of the ACC in regulating postnatal and adult neurogenesis in these regions are still insufficiently explored. Investigating the intricate involvement of the ACC in neurogenesis could enhance our comprehension of essential aspects of brain plasticity. This involvement stems from its complex circuitry with other relevant brain regions, thereby exerting both direct and indirect impacts on the neurogenesis process. This review sheds light on the promising significance of the ACC in orchestrating postnatal and adult neurogenesis in conditions related to memory, cognitive behavior, and associated disorders.

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The impact of chronic fluoxetine treatment in adolescence or adulthood on context fear memory and perineuronal nets

Chan,

Baker,

Richardson

2024

Developmental Psychobiology

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Selective serotonin reuptake inhibitors, such as fluoxetine (Prozac), are commonly prescribed pharmacotherapies for anxiety. Fluoxetine may be a useful adjunct because it can reduce the expression of learned fear in adult rodents. This effect is associated with altered expression of perineuronal nets (PNNs) in the amygdala and hippocampus, two brain regions that regulate fear. However, it is unknown whether fluoxetine has similar effects in adolescents. Here, we investigated the effect of fluoxetine exposure during adolescence or adulthood on context fear memory and PNNs in the basolateral amygdala (BLA), the CA1 subregion of the hippocampus, and the medial prefrontal cortex in rats. Fluoxetine impaired context fear memory in adults but not in adolescents. Further, fluoxetine increased the number of parvalbumin (PV)‐expressing neurons surrounded by a PNN in the BLA and CA1, but not in the medial prefrontal cortex, at both ages. Contrary to previous reports, fluoxetine did not shift the percentage of PNNs toward non‐PV cells in either the BLA or CA1 in the adults, or adolescents. These findings demonstrate that fluoxetine differentially affects fear memory in adolescent and adult rats but does not appear to have age‐specific effects on PNNs.

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Activity of the anterior cingulate cortex and ventral hippocampus underlie increases in contextual fear generalization

Cited by 92 publications

References 41 publications

Hippocampal GABAB(1a) Receptors Constrain Generalized Contextual Fear

Hippocampal GABAB(1a) Receptors Constrain Generalized Contextual Fear

Significance of the anterior cingulate cortex in neurogenesis plasticity: Connections, functions, and disorders across postnatal and adult stages

The impact of chronic fluoxetine treatment in adolescence or adulthood on context fear memory and perineuronal nets

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