Maternal deprivation induces alterations in cognitive and cortical function in adulthood

Abstract

Early life trauma is a risk factor for a number of neuropsychiatric disorders, including schizophrenia (SZ). The current study assessed how an early life traumatic event, maternal deprivation (MD), alters cognition and brain function in rodents. Rats were maternally deprived in the early postnatal period and then recognition memory (RM) was tested in adulthood using the novel object recognition task. The expression of catechol-o-methyl transferase (COMT) and glutamic acid decarboxylase (GAD67) were quantified in the medial prefrontal cortex (mPFC), ventral striatum, and temporal cortex (TC). In addition, depth EEG recordings were obtained from the mPFC, vertex, and TC during a paired-click paradigm to assess the effects of MD on sensory gating. MD animals exhibited impaired RM, lower expression of COMT in the mPFC and TC, and lower expression of GAD67 in the TC. Increased bioelectric noise was observed at each recording site of MD animals. MD animals also exhibited altered information theoretic measures of stimulus encoding. These data indicate that a neurodevelopmental perturbation yields persistent alterations in cognition and brain function, and are consistent with human studies that identified relationships between allelic differences in COMT and GAD67 and bioelectric noise. These changes evoked by MD also lead to alterations in shared information between cognitive and primary sensory processing areas, which provides insight into how early life trauma confers a risk for neurodevelopmental disorders, such as SZ, later in life.

An Emergent Discriminative Learning Is Elicited During Multifrequency Testing

“…Previous studies have demonstrated the involvement of the mPFC in the regulation of conditioned fear learning (Resstel et al, 2006; Almada et al, 2013; Marek et al, 2018; Spalding, 2018). Although mPFC neurons respond to noise (Bubser and Koch, 1994; Kim et al, 2009; Likhtik et al, 2014), clicks (Mihalick et al, 2001; Martin-Cortecero and Nunez, 2016; Janetsian-Fritz et al, 2018) and pure tones (Sierra-Mercado et al, 2006; Fenton et al, 2014; Likhtik et al, 2014), iso-frequency pure tones such as 3 kHz (Fenton et al, 2014), 4 kHz (Sierra-Mercado et al, 2006), and 8 kHz (Likhtik et al, 2014) have been used as CSs in conditioned fear learning. Since there has been no further study on the frequency response properties of mPFC neurons to pure tones, the pure tone responses of mPFC neurons and whether they change after auditory fear conditioning, as well as the connection between the sound responses of mPFC neurons and any hypothetical emergent discriminative learning, remain unclear.…”

Schizophrenia, the gut microbiota, and new opportunities from optogenetic manipulations of the gut-brain axis

“…Regarding the postnatal risk factors, many studies focused on early life stress, such as malnutrition and maternal separation [ 40 , 51 ]. Remarkably, animal models of maternal deprivation have been used to address several behavioral and neurochemical changes in the offspring’s brains.…”

Application of animal experimental models in the research of schizophrenia

“…Recent studies have found that animals having undergone mother‐to‐child separation also show impaired recognition memory. The expression of both the Catechol‐O‐methyltransferase (COMT) in the medial prefrontal cortex and temporal cortex, and glutamic acid decarboxylase 67 (GAD67) in the temporal cortex enzyme 67 are reduced (Janetsian‐Fritz et al, 2018). Other studies have shown that chronic use of clozapine can reverse the learning deficit of this rat model rat in the T maze test (Li, Wu, & Li, 2007), and the antipsychotic drug raclopride can reverse prepulse inhibition (PPI) deficiency.…”