1. INTRODUCTION
Genetic variation is an important factor for individual variability in cognitive and neuropsychiatric traits (Deary et al. , 2009; Avshalom et al. , 2010; Ressler et al. , 2011). Specific inbred mouse strains provide useful models to study neurobiological correlates of such complex behavioural traits and their interaction with a certain genetic background. To date, while there is abundant evidence for altered emotional and cognitive phenotypes among widely used inbred mouse strains (Radulovic et al. , 1998; Stiedl et al. , 1999; Contet et al. , 2001; Rodgers et al. , 2002; Siegmundet al. , 2005; Bryant et al. , 2008; Camp et al. , 2009, 2012; Temme et al. , 2014; March et al. , 2014; Åhlgren & Voikar, 2019; Sloin et al. , 2022), electrophysiological correlates of such phenotypic characteristics are only limited to classical measurements of synaptic plasticity using hippocampal slice preparations (Nguyen, Abel, et al. , 2000; Nguyen, Duffy, et al. , 2000; Gerlai, 2002; Schimanski et al. , 2007; Freund et al. , 2016).
Of note, brain oscillations are thought to be involved in diverse emotional and cognitive functions (Buzsáki & Watson, 2012). Such oscillatory patterns with varying frequency ranges can be recorded robustly in the hippocampus in vivo and in vitro . Specifically, gamma oscillations (30-100 Hz) have been shown to support maintenance of working memory and attention (Fries et al. , 2001; Montgomery & Buzsáki, 2007). Their generation and sustainment primarily depend on the cholinergic level (Fisahn et al. , 1998; Vandecasteele et al. , 2014; Caliskan et al. , 2015). Accordingly, in vivo optogenetic activation of septo-hippocampal cholinergic fibres also triggers gamma oscillations in the hippocampus (Vandecasteele et al. , 2014). Importantly, “cholinergic” gamma-range oscillations can be induced in hippocampal slice preparations upon exposure to type 1 muscarinic acetylcholine (M1-) receptor agonists (Fisahn et al. , 1998). On the other hand, during reduced neuromodulation (e.g., slow wave sleep, quite wakefulness) gamma oscillations are replaced by sharp wave-ripples (SW-R; (Buzsáki et al. , 1992; Ylinen et al. , 1995). These transient events occur at rate of 0.01-2 Hz together with superimposed fast ripples in the hippocampal CA1 (150-250 Hz) (Buzsaki, 1989; Ylinenet al. , 1995; Csicsvari et al. , 2000). Similarly, in slice preparations of ventral-to-mid hippocampus, spontaneous SW-R appear in the CA3 and propagate along the CA1/subiculum axis (Maier et al. , 2003; Maslarova et al. , 2015; Çalışkan et al. , 2016). Convincing evidence indicates that these transients are involved in the reactivation of cellular activity patterns associated with a learning period and support both spatial and emotional memory consolidation (Wilson & McNaughton, 1994; Kudrimoti et al. , 1999; Girardeauet al. , 2017). Their targeted disruption impairs both spatial memory and contextual fear memory (Girardeau et al. , 2009; Wanget al. , 2015).
Most of the brain rhythms including gamma oscillations and SW-R are inhibition-based with complex involvement of different types of GABAergic interneurons that provide rhythmic inhibition to excitatory principal neurons (Hájos et al. , 2004; Hájos & Paulsen, 2009; Buzsáki & Watson, 2012). Among many different types of GABAergic interneurons, particular attention has been given to the involvement of parvalbumin-positive (PV+) and somatostatin (SST+) interneurons in generation and modulation of hippocampal network oscillations (Starket al. , 2014; Norimoto et al. , 2018; Antonoudiou et al. , 2020). Notably, hippocampal CA3 subregion is able to generate robust oscillations due to strong recurrent collaterals among principal cells and their interaction with local interneurons forming an associative network (Le Duigou et al. , 2014).
To the best of our knowledge only a handful of studies have systematically investigated possible alterations in hippocampal network oscillations in inbred mouse strains with a main focus on gamma oscillations in vitro (Jansen et al. , 2009; Heisteket al. , 2010). Intriguingly, no previous work have explored hippocampal SW-R in common inbred mouse strains. Therefore, we studied hippocampal network oscillations in three commonly used inbred mouse strains: C57BL/6J (B6J), C57BL/6NCrl (B6N) and 129S2/SvPasCrl (129) with the goal to identify common oscillatory features in inbred mouse strains that show aberrant fear and anxiety (B6N and 129) and compare them to B6J strain. We further performed immunohistochemical analysis of main GABAergic interneuron populations and measured CA3 associative network activation using extracellular electrophysiology. We identified several common oscillatory features in B6N and 129 inbred mouse strains, however, with diverging interneuronal and CA3 associative network phenotypes. Our results suggest that in vitro hippocampal network oscillations can be used to study neurobiological correlates of phenotypic differences among common inbred mouse strains similar to previously reported classical measures of synaptic plasticity in hippocampal slices.