scholarly journals Fast Spiking and Regular Spiking Neural Correlates of Fear Conditioning in the Medial Prefrontal Cortex of the Rat

2001 ◽  
Vol 11 (5) ◽  
pp. 441-451 ◽  
Author(s):  
E. H. Baeg
2018 ◽  
Author(s):  
Karthik R. Ramanathan ◽  
Reed L. Ressler ◽  
Jingji Jin ◽  
Stephen Maren

AbstractThe nucleus reuniens (RE) is a ventral midline thalamic nucleus that interconnects the medial prefrontal cortex (mPFC) and hippocampus (HPC). Considerable data indicate that HPC-mPFC circuits are involved in contextual and spatial memory; however, it is not clear whether the RE mediates the acquisition or retrieval of these memories. To examine this question, we inactivated the RE with muscimol before either the acquisition or retrieval of Pavlovian fear conditioning in rats; freezing served as the index of fear. We found that RE inactivation before conditioning impaired the acquisition of contextual freezing, whereas inactivation of the RE prior to retrieval testing increased the generalization of freezing to a novel context; inactivation of the RE did not affect either the acquisition or expression of auditory fear conditioning. Interestingly, contextual conditioning impairments were absent when retrieval testing was also conducted after RE inactivation. Contextual memories acquired under RE inactivation were hippocampal-independent, insofar as contextual freezing in rats conditioned under RE inactivation was insensitive to intra-hippocampal infusions of the NMDA receptor antagonist, D,L-amino-5-phosophonovaleric acid (APV). Together, these data reveal that the RE supports hippocampal-dependent encoding of precise contextual memories that allow discrimination of dangerous from safe contexts. When the RE is inactive, however, alternate neural systems acquire an impoverished contextual memory that is only expressed when the RE is offline.SIGNIFICANCE STATEMENTThe midline thalamic nucleus reuniens (RE) coordinates communication between the hippocampus and medial prefrontal cortex, brain areas critical for contextual and spatial memory. Here we show that temporary pharmacological inactivation of RE impairs the acquisition and precision of contextual fear memories after Pavlovian fear conditioning in rats. However, inactivating the RE prior to retrieval testing restored contextual memory in rats conditioned after RE inactivation. Critically, we show that imprecise contextual memories acquired under RE inactivation are learned independently of the hippocampus. These data reveal that the RE is required for hippocampal-dependent encoding of precise contextual memories to support the discrimination of safe and dangerous contexts.


2020 ◽  
Vol 15 (9) ◽  
pp. 941-949
Author(s):  
Laura Finlayson-Short ◽  
Christopher G Davey ◽  
Ben J Harrison

Abstract Self-referential and social processing are often engaged concurrently in naturalistic judgements and elicit activity in overlapping brain regions. We have termed this integrated processing ‘self-other referential processing’ and developed a task to measure its neural correlates. Ninety-eight healthy young people aged 16–25 (M = 21.5 years old, 67% female) completed our novel functional magnetic resonance imaging task. The task had two conditions, an active self-other referential processing condition in which participants rated how much they related to emotional faces and a control condition. Rating relatedness required thinking about oneself (self-referential processing) and drawing a comparison to an imagined other (social processing). Self-other referential processing elicited activity in the default mode network and social cognition system; most notably in the ‘core self’ regions of the medial prefrontal cortex and posterior cingulate cortex. Relatedness and emotional valence directly modulated activity in these core self areas, while emotional valence additionally modulated medial prefrontal cortex activity. This shows the key role of the medial prefrontal cortex in constructing the ‘social-affective self’. This may help to unify disparate models of medial prefrontal cortex function, demonstrating its role in coordinating multiple processes—self-referential, social and affective processing—to allow the self to exist in a complex social world.


2020 ◽  
Author(s):  
John H. Harkness ◽  
Angela E. Gonzalez ◽  
Priyanka N. Bushana ◽  
Emily T. Jorgensen ◽  
Deborah M. Hegarty ◽  
...  

ABSTRACTPerineuronal nets (PNNs) surrounding fast-spiking, parvalbumin (PV) inhibitory interneurons are vital for providing excitatory:inhibitory balance within cortical circuits, and this balance is impaired in disorders such as schizophrenia, autism spectrum disorder, and substance use disorders. These disorders are also associated with altered diurnal rhythms, yet few studies have examined the diurnal rhythms of PNNs or PV cells. We measured the intensity and number of PV cells and PNNs labeled with Wisteria floribunda agglutinin (WFA) in the rat prelimbic medial prefrontal cortex (mPFC) at Zeitgeber times (ZT) ZT0, 6, 12, and 18. We also measured the oxidative stress marker 8-oxo-deoxyguanosine (8-oxo-dG). Relative to ZT0, the intensities of PNN and PV staining were increased in the dark (active) phase compared with the light (inactive) phase. The intensity of 8-oxo-dG was decreased from ZT0 at all time points (ZT6,12,18), in both PV cells and non-PV cells. To examine corresponding changes in inhibitory and excitatory inputs, we measured GAD 65/67 and vGlut1 puncta apposed to PV cells with and without PNNs. Relative to ZT6, there were more excitatory puncta on PV cells surrounded by PNNs at ZT18, but no changes in PV cells devoid of PNNs. No changes in inhibitory puncta were observed. Whole-cell slice recordings in fast-spiking (PV) cells with PNNs showed an increased ratio of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor:N-methyl-D-aspartate receptor (AMPA:NMDA) at ZT18 vs. ZT6. The number of PV cells and co-labeled PV/PNN cells containing the transcription factor orthodenticle homeobox 2 (OTX2), which maintains PNNs, showed a strong trend toward an increase from ZT6 to ZT18. These diurnal fluctuations in PNNs and PV cells are expected to alter cortical excitatory:inhibitory balance and provide new insights into treatment approaches for diseases impacted by imbalances in sleep and circadian rhythms.


2019 ◽  
Vol 237 (1) ◽  
pp. 231-248 ◽  
Author(s):  
Joachim Latusz ◽  
Marzena Maćkowiak

Abstract Rationale Several findings indicate that early-life dysfunction of N-methyl-d-aspartate (NMDA) receptors might cause schizophrenia-like abnormalities in adulthood that might be induced by impairments in epigenetic regulation. Objectives In the present study, we investigated whether postnatal blockade of NMDA receptors (within the first 3 weeks of life) by the competitive antagonist CGP 37849 (CGP) might affect some epigenetic markers in the adult medial prefrontal cortex (mPFC). Methods Histone H3 phosphorylation at serine 10 (H3S10ph), histone H3 acetylation at lysine 9 or 14 (H3K9ac or H3K14ac, respectively), or expression of histone deacetylase (HDAC) 2, HDAC5, myocyte enhancer factor (MEF) 2D and activity-regulated cytoskeleton-associated protein (Arc) were analysed. Moreover, we also evaluated whether the deacetylase inhibitor sodium butyrate (SB; 1.2 mg/kg, ip) could prevent behavioural and neurochemical changes in the mPFC induced by CGP during memory retrieval in the trace fear conditioning paradigm. Results The results showed that CGP administration increased the number of H3S10ph nuclei but did not affect H3K9ac and H3K14ac or HDAC2 protein levels. However, CGP administration altered the HDAC5 mRNA and protein levels and increased the mRNA and protein levels of MEF2D. CGP also increased Arc mRNA, which was correlated with an increase in the amount of Arc DNA bound to MEF2D. SB given 2 h after training prevented impairment of the freezing response and disruption of epigenetic markers (H3S10ph, HDAC5, MEF2D) and Arc expression during memory retrieval induced by CGP administration. Conclusions The early-life blockade of NMDA receptors impairs some epigenetic regulatory processes in the mPFC that are involved in fear memory formation.


Sign in / Sign up

Export Citation Format

Share Document