Structural Correlates of CA2 and CA3 Pyramidal Cell Activity in Freely-Moving Mice

Abstract

Plasticity within hippocampal circuits is essential for memory functions. The hippocampal CA2/CA3 region is thought to be able to rapidly store incoming information by plastic modifications of synaptic weights within its recurrent network. Highfrequency spike-bursts are believed to be essential for this process, by serving as triggers for synaptic plasticity. Given the diversity of CA2/CA3 pyramidal neurons, it is currently unknown whether and how burst activity, assessed in vivo during natural behavior, relates to principal cell heterogeneity. To explore this issue, we juxtacellularly recorded the activity of single CA2/CA3 neurons from freely-moving male mice, exploring a familiar environment. In line with previous work, we found that spatial and temporal activity patterns of pyramidal neurons correlated with their topographical position. Morphometric analysis revealed that neurons with a higher proportion of distal dendritic length displayed a higher tendency to fire spikebursts. We propose that the dendritic architecture of pyramidal neurons might determine burst-firing by setting the relative amount of distal excitatory inputs from the entorhinal cortex.

In VivoCalcium Imaging of CA3 Pyramidal Neuron Populations in Adult Mouse Hippocampus

“…We estimate that the especially large and prolonged calcium events that we observed were caused by >30 APs over 3 s, indicating that a subset of CA3 pyramidal neurons can sustain firing rates of 10 Hz or higher during running. This spiking level is not too dissimilar from in-field firing rates observed in identified CA3 place cells (Mizuseki et al, 2012;Ding et al, 2020). As our experiments were conducted in the dark without salient spatial cues, we can only speculate that these events may relate to place cell or time cell properties.…”

Nitrergic modulation of neuronal excitability in the mouse hippocampus is mediated via regulation of Kv2 and voltage‐gated sodium channels

“…The findings reported in our study may also have implications for regulating neuronal excitability following acute changes in hippocampal firing patterns and activity‐driven NO generation, such as occur during traumatic brain injuries, epileptiform or changes in temporal spiking properties during fundamental computational activities (Ding et al, 2020; Ghotbeddin et al, 2019; Karimi et al, 2020; Martin et al, 2019; Song et al, 2020).…”

In vivo calcium imaging of CA3 pyramidal neuron populations in adult mouse hippocampus

“…<0.001, one-way ANOVA (small events: panesth./run = 1.7×10 -4 , prest/run = 4.5×10 -16 ; large events: prest/run = 6.7×10 -6 ). (Henze et al, 2002;Frerking et al, 2005;Wittner and Miles, 2007;Mizuseki et al, 2012;Kowalski et al, 2016;Oliva et al, 2016Ding et al, 2020. Compared to DG granule cells (Pilz et al, 2016) a much higher fraction of CA3 pyramidal neurons displayed clear calcium transients (>90% for all conditions in CA3; for comparison: <10% during anesthesia and around 50% during wakefulness in DG).…”

“…The functional properties of CA3 pyramidal neurons have been characterized largely with electrophysiology, using extracellular recordings ( Fox and Ranck, 1975;Csicsvari et al, 2000;Henze et al, 2002;Leutgeb et al, 2004;Frerking et al, 2005;Mizuseki et al, 2012, Oliva et al, 2016, in vivo intra-and juxtacellular recordings (Epsztein et al, 2011;Kowalski et al, 2016;Zucca et al, 2017;Diamantaki et al, 2018;Hunt et al, 2018;Malezieux et al, 2020), and whole-cell recordings in brain slices (Jonas et al, 1993;Hemond et al, 2008;Hunt et al, 2018;Raus Balind et al, 2019). Pyramidal neurons in CA3 show properties distinct from CA1 (Mizuseki et al, 2012;Oliva et al, 2016) but display heterogeneity within their population (Cembrowski and Spruston, 2019;Ding et al, 2020;Hunt et al, 2018). For CA3 pyramidal neurons, mean firing rates typically range from 0.3 to 5 Hz in vivo (Henze et al, 2002;Wittner and Miles, 2007;Mizuseki et al, 2012;Kowalski et al, 2016;Oliva et al, 2016;Ding et al, 2020), lower than for CA1 pyramidal neurons but higher when compared to dentate gyrus (DG) granule cells.…”

“…Pyramidal neurons in CA3 show properties distinct from CA1 (Mizuseki et al, 2012;Oliva et al, 2016) but display heterogeneity within their population (Cembrowski and Spruston, 2019;Ding et al, 2020;Hunt et al, 2018). For CA3 pyramidal neurons, mean firing rates typically range from 0.3 to 5 Hz in vivo (Henze et al, 2002;Wittner and Miles, 2007;Mizuseki et al, 2012;Kowalski et al, 2016;Oliva et al, 2016;Ding et al, 2020), lower than for CA1 pyramidal neurons but higher when compared to dentate gyrus (DG) granule cells. As a prominent feature, hippocampal pyramidal neurons, especially in CA3, exhibit bursts of action potentials (APs) with inter-spike intervals <6 ms (Fox and Ranck, 1975;Frerking et al, 2005;Mizuseki et al, 2012;Kowalski et al, 2016;Oliva et al, 2016;Raus Balind et al, 2019).…”