Elsevier

Brain Research

Volume 1325, 14 April 2010, Pages 77-88
Brain Research

Research Report
Inactivation or inhibition of neuronal activity in the medial prefrontal cortex largely reduces pup retrieval and grouping in maternal rats

https://doi.org/10.1016/j.brainres.2010.02.027Get rights and content

Abstract

Previous research suggests that the maternal medial prefrontal cortex (mPFC) may play a role in maternal care and that cocaine sensitization before pregnancy can affect neuronal activity within this region. The present work was carried out to test whether the mPFC does actually play a role in the expression of maternal behaviors in the rats and to understand what specific behaviors this cortical area may modulate. In the first experiment, tetrodotoxin (TTX) was used to chemically inactivate the mPFC during tests for maternal behavior latencies. Lactating rats were tested on postpartum days 7–9. The results of this first experiment indicate that there is a large effect of TTX-induced inactivation on retrieval behavior latencies. TTX nearly abolished the expression of maternal retrieval of pups without significantly impairing locomotor activity. In the second experiment, GABA-mediated inhibition was used to test maternal behavior latencies and durations of maternal and other behaviors in postpartum dams. In agreement with experiment 1, it was observed that dams capable of retrieving are rendered incapable by inhibition in the mPFC. GABA-mediated inhibition in the mPFC largely reduced retrieval without altering other indices of maternal care and non-specific behavior such as ambulation time, self-grooming, and inactivity. Moreover, in both experiments, dams were able to establish contact with pups within seconds. The overall results indicate that the mPFC may play an active role in modulating maternal care, particularly retrieval behavior. External factors that affect the function of the frontal cortical site may result in significant impairments in maternal goal-directed behavior as reported in our earlier work.

Introduction

Subcortical neural circuits that mediate the expression of maternal behaviors have been studied in detail across different species of mammals and using various in vivo and ex vivo techniques. In the rat, retrieval, nest building, and pup licking are maternal behaviors that involve the medial preoptic area (mPOA), ventral pallidum (VP), bed nucleus of stria terminalis (BNST), ventral tegmental area (VTA), the shell and core of the nucleus accumbens (NAC), medial and central amygdala, and the olfactory system (Fleming and Walsh, 1994, Lee et al., 1999, Li & Fleming, 2003, Numan et al., 1977, Numan & Smith, 1984, Numan et al., 2005b, Numan, 2007, Stack et al., 2002). Kyphotic nursing and nest aggression are associated with neuronal activity in the periaqueductal grey and has also been associated to a diversity of sensory inputs from pups (Kolunie et al., 1994, Lonstein & Stern, 1997a, Lonstein & Stern, 1997b, Lonstein et al., 1998b, Lonstein & Stern, 1998, Stern & Mackinnon, 1978, Stern and Johnson, 1989; Stern & Kolunie, 1993, Stern & Lonstein, 2001). Although less attention has been placed recently on the role of the cerebral cortex in maternal behaviors, there has been considerable historical interest in its participation in multisensory processing and in controlling subcortical outputs leading to maternal care. Beach, 1937, Stone, 1938 observed that removal of 1–50% cortical tissue was sufficient to dramatically affect maternal behavior, especially pup retrieval, and this was not merely due to inability to physically move pups. Slotnick and Nigrosh (Slotnick, 1967, Slotnick & Nigrosh, 1975) and Stamm (1955) showed that removal of medial aspects of cerebral cortex, including most of the anterior and posterior cingulate cortex, reduces maternal care, observing predominant reductions in retrieval behavior, in rats and mice. A similar impact of midline cortical ablation on retrieval behavior has been observed in other species of rodents (Murphy et al., 1981). Much more recently, Afonso et al. (2007) showed that pre-pregnancy excitotoxic lesions of the medial prefrontal cortex (mPFC, including prelimbic and infralimbic areas) significantly alter both sexual and maternal behaviors in female rats. Therefore, the timing of the selective damage to this cortical area before pregnancy can still impair the ability to subsequently express maternal behaviors. It is unclear whether affecting the neuronal activity in mPFC after parturition might also lead to a similar influence on maternal behaviors. If so, then GABA-mediated inhibition or chemical inactivation of the mPFC during the postpartum period should affect maternal behavior expression.

Using functional MRI, Febo & Ferris, 2007, Ferris et al., 2005 previously reported increased neuronal activity in mPFC in response to suckling stimulation from pups. Activity in the maternal prefrontal cortex in response to suckling pups was dramatically reduced by cocaine sensitization before pregnancy. Animals pretreated with cocaine were also observed to display greater levels of retrieval behavior, but a direct causal link between changes in prefrontal cortical activity and retrieval behavior was not provided (Febo and Ferris, 2007). However, the results from this latter study did suggest that limbic regions of the prefrontal cortex may play a role in retrieval and other maternal behaviors and that its role may be adversely affected by cocaine sensitization (Febo and Ferris, 2007). In human functional MRI studies, there is also evidence of a role for limbic prefrontal regions in maternal care. Mother's responding to infant sensory cues showed BOLD activity in areas of the limbic prefrontal cortex such as the anterior cingulate, insula, orbital, and ventromedial frontal regions (Bartels & Zeki, 2000, Leibenluft et al., 2004, Lorberbaum et al., 2002, Nitschke et al., 2004, Noriuchi et al., 2008, Ranote et al., 2004, Strathearn et al., 2008, Swain et al., 2008). In the present study, we tested whether neuronal activity in mPFC participates in the expression of maternal care in rat. This was accomplished by localized inactivation with tetrodotoxin or GABA-mediated inhibition of the medial PFC before testing for maternal behaviors. Given the wealth of anatomical data demonstrating connectivity of prefrontal cortical areas with key limbic subcortical sites such as the olfactory cortex, hypothalamus, amygdala, and nucleus accumbens (Hoover & Vertes, 2007, Ongur et al., 1998, Ongur & Price, 2000, Ongur et al., 2003, Vertes, 2002, Vertes, 2004), we hypothesized that neuronal activity within mPFC would heavily influence the expression of postpartum maternal behaviors.

Section snippets

Experiment 1: TTX inactivation of mPFC dramatically reduces drive to retrieve pups

TTX or aCSF was infused into the mPFC of dams 25–30 min before testing for latencies to express several maternal behaviors. By chemically inactivating sodium channel conductance on neurons located in mPFC using TTX, we anticipated a suppression of neuronal activity within this cortical region that would allow us to test for changes in maternal behaviors.

Dams were able to notice and attend to the presence of pups within the cage regardless of pretreatment. After returning pups to the home cage,

Discussion

The present work provides significant evidence that neuronal activity in mPFC is important in maternal care. Moreover, it appears that activity of neurons in this cortical structure is important for expression of retrieval behavior. We observed that inactivation of mPFC results in a dramatic reduction in retrieval behavior without a significant loss of locomotor activity in response to a novel environment or the ability to detect and contact pups within the home cage. Inhibition of mPFC through

Subjects

Adult Long–Evans female rats (225–275 g; 70–120 days old) were purchased from Charles River Laboratories (Wilmington, MA). Animals were housed in pairs in a temperature and humidity controlled room and maintained on a 12:12 light–dark cycle (lights on at 0700–1900 h). Water and Purina rat chow were provided ad libitum. Home cages consisted of hanging plastic microisolater cages of standard dimensions with woodchip bedding. After mating, dams were housed individually along with their litters. All

Acknowledgments

This study was supported by a grant from National Institute on Drug Abuse (DA019946) to MF. Its contents are solely the responsibility of the authors and do not represent the official views of the NIDA. T.R.J. is recipient of an undergraduate Provost research award at Northeastern University.

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