Abstract
The ability to distill specific frequencies from complex spatiotemporal patterns of afferent inputs is a pivotal functional requirement for neurons residing in networks receiving frequency-multiplexed inputs. Although the expression of theta-frequency subthreshold resonance is established in hippocampal pyramidal neurons, it is not known if their spike initiation dynamics manifest spectral selectivity, or if their intrinsic properties are tuned to process gamma-frequency inputs. Here, we measured the spike-triggered average (STA) of rat hippocampal pyramidal neurons through electrophysiological recordings and quantified spectral selectivity in their spike initiation dynamics and their coincidence detection window (CDW). Our results revealed strong theta-frequency selectivity in the STA, which was also endowed with gamma-range CDW, with prominent neuron-to-neuron variability that manifested distinct pairwise dissociations and correlations with different intrinsic measurements. Furthermore, we demonstrate that the STA and its measurements substantially adapted to the state of the neuron defined by its membrane potential and to the statistics of its afferent inputs. Finally, we tested the effect of pharmacologically blocking the hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels on the STA and found that the STA characteristic frequency reduced significantly to the delta-frequency band after HCN channel blockade. This delta-frequency selectivity in the STA emerged in the absence of subthreshold resonance, which was abolished by HCN channel blockade, thereby confirming computational predictions on the dissociation between these two forms of spectral selectivity. Our results expand the roles of HCN channels to theta-frequency selectivity in the spike initiation dynamics, apart from underscoring the critical role of interactions among different ion channels in regulating neuronal physiology.NEW & NOTEWORTHY We had previously predicted, using computational analyses, that the spike-triggered average (STA) of hippocampal neurons would exhibit theta-frequency (4-10 Hz) spectral selectivity and would manifest coincidence detection capabilities for inputs in the gamma-frequency band (25-150 Hz). Here, we confirmed these predictions through direct electrophysiological recordings of STA from rat CA1 pyramidal neurons and demonstrate that blocking HCN channels reduces the frequency of STA spectral selectivity to the delta-frequency range (0.5-4 Hz).
Highlights
NEW & NOTEWORTHY We had previously predicted, using computational analyses, that the spike-triggered average (STA) of hippocampal neurons would exhibit theta-frequency (4 –10 Hz) spectral selectivity and would manifest coincidence detection capabilities for inputs in the gamma-frequency band (25–150 Hz)
Whereas the total CDW was more reflective of the membrane time constant of these neurons, the effective CDW, which accounts for the shape of the STA, was in the gammafrequency range
Prior modeling results corresponding to hippocampal somatic STA (Fig. 7 of Das and Narayanan 2015) had predicted ISpeTaAk to be ~200 pA, fSTA to be in the theta-range ~5 Hz (Fig. 2A: 3–7 Hz), QSTA to be ~1.2 (Fig. 2A: 1.2–2.2), total CDW (TTCDW) to be ~45 ms (Fig. 2A: 20 – 60 ms), and the effective CDW (TECDW) to be ~11 ms (Fig. 2A: 6 –18 ms), which are within the ranges obtained with our current electrophysiological measurements
Summary
NEW & NOTEWORTHY We had previously predicted, using computational analyses, that the spike-triggered average (STA) of hippocampal neurons would exhibit theta-frequency (4 –10 Hz) spectral selectivity and would manifest coincidence detection capabilities for inputs in the gamma-frequency band (25–150 Hz) We confirmed these predictions through direct electrophysiological recordings of STA from rat CA1 pyramidal neurons and demonstrate that blocking HCN channels reduces the frequency of STA spectral selectivity to the delta-frequency range (0.5– 4 Hz). In assessing the relationship between the STA, neuronal feature selectivity, and coincidence detection, recent studies have derived STA-based quantitative metrics that could be used to assess neuronal suprathreshold frequency selectivity and coincidence detection window (CDW) These computational studies demonstrated a clear dependence of STA-based metrics on channel expression profiles, with specific channels capable of effectuating transitions that span the integratorcoincidence detector continuum characterized by the class of STA (Das et al 2017; Das and Narayanan 2014, 2015). HCN channels have been shown to play several critical neurophysiological roles in regulating resting membrane potential (RMP) (Gasparini and DiFrancesco 1997; Magee 1998; Mishra and Narayanan 2015; Poolos et al 2002), neuronal excitability (Brager and Johnston 2007; Fan et al 2005; Gasparini and DiFrancesco 1997; Magee 1998; Mishra and Narayanan 2015; Narayanan et al 2010; Narayanan and Johnston 2007; Poolos et al 2002; van Welie et al 2004), temporal summation (Magee 1998, 1999b, 2000; Williams and Stuart 2000), subthreshold resonance (Hu et al 2009, 2002; Hutcheon et al 1996a, 1996b; Hutcheon and Yarom 2000; Narayanan and Johnston 2007), neuronal oscillations (Dickson et al 2000; Fransén et al 2004; Lüthi and McCormick 1998a, 1998b), somatodendritic coupling (Cook et al 2007; Hu et al 2009; Ulrich 2002; Vaidya and Johnston 2013), intrinsic phase response (Marcelin et al 2009; Narayanan and Johnston 2008; Rathour and Narayanan 2012, 2014; Vaidya and Johnston 2013), synaptic plasticity profiles (Anirudhan and Narayanan 2015; Honnuraiah and Narayanan 2013; Narayanan and Johnston 2010; Nolan et al 2004), local field potentials (LFPs) (Ness et al 2016; Sinha and Narayanan 2015), and neuronal spike phases with reference to external oscillations and their coherence (Sinha and Narayanan 2015)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
