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.