Stathmin reveals dissociable roles of the basolateral amygdala in parental and social behaviors

Abstract

Innate parental behaviors and adult social interactions are essential for survival of the individual along with the species as a whole. Because these behaviors require threat assessment of the environment, it is plausible that they are regulated by the amygdalaassociated neural circuitry of fear. However, the amygdala is not a single anatomic and functional unit, and nuclei of the amygdala have multiple inter-and intra-connections. This poses a question as to the exact role of different amygdala nuclei in these behaviors and the mechanisms involved. The basolateral complex of the amygdala nuclei (BLA) is particularly interesting in this regard: although the BLA role in forming memories for learned fear is established, the BLA role in innate behaviors is not well understood. We recently demonstrated that mice without an inhibitor of microtubules, stathmin, a gene enriched in BLA-associated circuitry, have deficiency in innate and learned fear. Here we show that the deficiency in fear processing in stathmin ؊/؊ females leads to improper threat assessment, which in turn affects innate parental care and adult social interactions. Profound deficiency is observed in maternal behavior of stathmin ؊/؊ females: they lack motivation for retrieving pups and are unable to choose a safe location for nest-building. Remarkably, stathmin ؊/؊ females have an enhancement in social interactions. BLA lesions in WT mice produce similar effects in maternal and social behaviors, confirming vital BLA participation. The findings implicate stathmin as the critical molecular component linking the BLA-associated neural circuitry with innate parental behaviors and adult social interactions.amygdala-enriched genes ͉ maternal behavior ͉ fear ͉ threat ͉ pup retrieval A mong Niko Tinbergen's four ''whys,'' representing a framework for understanding animal behavior, the third why refers to the survival value of a behavior (1). As such, a proper threat assessment is crucial in guiding animal and human activities (2, 3). Danger detection is critically dependent on the amygdala (4) and its many nuclei have various neural connections throughout the brain (5-7). Recent work provides clear evidence that amygdala nuclei have different roles in fear-related and reward-related learned behaviors (8-12). Specifically, the basolateral complex of the amygdala nuclei (throughout the article we refer to the lateral, or LA, and basal, or BA, nuclei as the basolateral complex, or BLA) is thought to be the major area of the brain involved in learned fear. However, little is known about the role of the BLA in other behaviors where danger assessment is essential. Unraveling the molecular, cellular, and anatomic mechanisms underlying the relationship between the BLA-associated circuitry and behaviors involving threat assessment may help to better understand behavioral choices in animals and humans.Here we examine the role of the BLA in two behaviors vital for individual safety and species survival: affiliative maternal care and adult social interactions. During mate...

Common and divergent psychobiological mechanisms underlying maternal behaviors in non-human and human mammals

“…Studies have shown that lesioning the basolateral amygdala (BLA) does not hasten maternal responding in nulliparous rats (Numan et al, 1993), and while numerous studies have found that lesioning or inactivating the BLA in pregnant or postpartum rodents and sheep has minor or transient effects on caregiving (Lee et al, 1999, 2000; Martel et al, 2008; Keller et al, 2004b), GABAA receptor antagonism in the BLA and adjacent basomedial nucleus do impair retrieval of pups (Numan et al, 2010). When the BLA does have effects on postpartum maternal behavior, it may do so by receiving sensory inputs from the young and potentiating activity of the mesolimbic system via projections to the nucleus accumbens and ventral palladum (Numan and Stolzenberg, 2009).…”

Deceivingly dynamic: Learning-dependent changes in stathmin and microtubules

“…In addition, stathmin knockout mice display enhanced extinction of cued fear conditioning, which was accompanied by an increase in neural activity in the prefrontal cortex and dentate gyrus with a simultaneous decrease in amygdala activity (Martel et al, 2012). Stathmin knockout mice also show an increase in social interactions but a decrease in social recognition memory and affiliative maternal care, which were associated with stathmin expression in the basolateral amygdala (Martel et al, 2008). Stathmin transgenic mice expressing Stat4A, an unphosphorylatable stathmin mutant, show reduced contextual fear memory (Uchida et al, 2014), suggesting that stathmin phosphorylation plays an important role in brain function.…”

“…Thus, it is not surprising that growing evidence links dysfunction in the adult brain to stathmin and microtubules. Stathmin has been implicated in abnormal states of fear, anxiety, cognition, social behavior, and brain trauma in rodents and humans (Brocke et al, 2010; Ehlis et al, 2011; Elder et al, 2012; Martel et al, 2012; Martel et al, 2008; Shumyatsky et al, 2005), suggesting microtubule involvement in these processes. Common single nucleotide polymorphisms (SNPs) in the STMN1 gene significantly impacted fear and anxiety responses in humans, measured with the startle and cortisol stress response (Brocke et al, 2010).…”

Learning and memory in Octopus vulgaris: a case of biological plasticity

“…In mammals, it is known that amygdala enriched stathmin is required for the expression of innate fear and the formation of memory for learned fear [67][68][69]. Interestingly, Ov-stm undergoes in the octopus to a negative regulation in response to fear conditioning.…”