Increased Prevalence of Calcium Transients across the Dendritic Arbor during Place Field Formation

Abstract

Summary Hippocampal place cell ensembles form a cognitive map of space during exposure to novel environments. However, surprisingly little evidence exists to support the idea that synaptic plasticity in place cells is involved in forming new place fields. Here we used high-resolution functional imaging to determine the signaling patterns in CA1 soma, dendrites and axons associated with place field formation when mice are exposed to novel virtual environments. We found that putative local dendritic spikes often occur prior to somatic place field firing. Subsequently, the first occurrence of somatic place field firing was associated with widespread regenerative dendritic events, which decreased in prevalence with increased novel environment experience. This transient increase in regenerative events was likely facilitated by a reduction in dendritic inhibition. Since regenerative dendritic events can provide the depolarization necessary for Hebbian potentiation, these results suggest that activity dependent synaptic plasticity underlies the formation of many CA1 place fields.

Transient effect of mossy fiber stimulation on spatial firing of CA3 neurons

“…It is also possible that mossy fiber inputs operate in different modes according to the requirement for new memory formation. Changes in excitation-inhibition balance, by modulatory inputs for example, may allow mossy fibers to impact CA3 pyramidal neurons differently in a novel environment (Ho, Zhang, & Skinner, 2009;Sheffield, Adoff, & Dombeck, 2017;Wilson & McNaughton, 1993), which remains to be tested.…”

Efficient phase coding in hippocampal place cells

“…6). However, it is important to note that the asymmetric afferent drive is just one of the physiological attributes that change with experience, with other attributes such as the somatodendritic inhibitory tone (Sheffield et al, 2017), the overall afferent drive and dendritically initiated spiking (Cohen et al, 2017) also exhibiting changes with experience. Although we report stimulus-dependent adaptation in the phase code that preserved its efficiency with the asymmetry, experience-dependence might alter or preserve the efficiency of the phase code through any of these other experience-dependent changes, which have not been incorporated into our model.…”

“…Although we report stimulus-dependent adaptation in the phase code that preserved its efficiency with the asymmetry, experience-dependence might alter or preserve the efficiency of the phase code through any of these other experience-dependent changes, which have not been incorporated into our model. Therefore, future models could assess experience-dependence of phase coding efficiency (and potential mechanisms that preserve efficiency) by accounting for all aspects of experience dependence, rather than assessing only asymmetric afferent drives (Mehta et al, 1997;Mehta et al, 2000;Mehta et al, 2002;Cohen et al, 2017;Sheffield et al, 2017).…”

Stability of excitatory structural connectivity predicts the probability of CA1 pyramidal neurons to become engram neurons

“…Especially in a brain region with high synaptic turnover such as hippocampal CA1 (Attardo et al, 2015;Pfeiffer et al, 2018), a bias towards structural synaptic stability might result in increased functional connectivity, which in turn would render a subset of neurons more receptive to memory allocation (Epsztein et al, 2011;Restivo et al, 2009;Sekeres et al, 2010). Moreover, increased synaptic transmission could lead to local plasticity (Losonczy and Magee, 2006;Losonczy et al, 2008) and prime CA1 PNs to become more active (Bittner et al, 2017;Sheffield et al, 2017). Further experiments should clarify the extent to which high structural stability leads to increased neuronal excitability.…”