Fernando R. Fernandez

Fernando R. Fernandez, PhD
BSc Neuroscience, University of Alberta
PhD Neuroscience, University of Calgary 2006
PhD Dissertation: The function of voltage-gated K+ conductances in neurons

Current Address & Contact Information:
Postdoctoral Fellow
Department of Bioengineering
University of Utah
20 South 2030 East 108 BPRB
Salt Lake City Utah 84112
f.fernandez@utah.edu

Training
1999
BSc Neuroscience
University of Alberta
Edmonton Alberta

2001 - 2006
PhD Neuroscience
University of Calgary
Calgary Alberta
Supervisor: R.W. Turner

2006
Methods in Computational Neuroscience
Woods Hole, MA

Awards
MSc
Province of Alberta Graduate Scholarship (2)
Teaching Assistantship

PhD
CIHR Doctoral Award
Dean's Research Excellence Award
CIHR Postdoctoral Fellowship

Research Focus: The biophysical properties of potassium channels underlying conditional backpropagation

Approach:

I use a combination of patch clamp recordings in vitro and conductance-based modeling to determine the relative contribution of different potassium channels to spike discharge and the input-output relation of pyramidal cells.

Preparations:

In vitro slice preparations, cDNA transfected expression systems (HEK, CHO), PC

Below are short summaries of my projects published from the Turner lab.

Model - ELL pyramidal cell burst discharge
Pyramidal cells of the electrosensory lobe (ELL) of weakly electric fish encode modulations in external electric fields by generating spike bursts. These bursts arise by a "conditional backpropagation" of sodium spikes from the soma and over the proximal apical dendrites that re-excite the soma as a depolarizing afterpotential (DAP). A frequency-dependent mismatch in refractory period between soma and dendrite leads to burst discharge through a cyclic failure of backpropagation. PDF

The kinetics of Kv3.3 potassium channels
Kv3.3 potassium channels were believed to exhibit a slow rate of inactivation, but resisted characterization due to difficulties associated with obtaining a reproducible rate of inactivation in expression systems. We showed that the variabilitiy in inactivation rate was due to a poor Kozak consensus sequence that could lead to leaky scanning by ribosomes. By introducing a strong Kozak sequence we showed that Kv3.3 channels are capable of inactivating in the same range as classic A-type potassium channels. See Fernandez et al. (2003). PDF

Obtaining patch clamp recordings in the adult CNS
Patch clamp recordings are often difficult to obtain beyond P17 due to a peri-neuronal net in the extracellular space. I helped develop a method of "spread-printing", a novel approach to partially dissociate tissue slices and remove the peri-neuronal net. We showed that spread-printing allows recordings from identified cells down to the single channel level in animals that are months old without the need for proteolytic enzymes. See Morales et al. (2004). PDF

Kv3 potassium channels exhibit frequency-dependent effects on cell output
This study describes a frequency-dependent effect of high threshold Kv3 potassium channels on the input-output relation of pyramidal cells and determined its underlying basis. A combination of patch recordings and modeling show that Kv3 channels rescue spike trains at high frequencies by decreasing both sodium channel inactivation and a cumulative increase in a low threshold potassium current. See Fernandez et al. (2005) PDF

A decrease in dendritic excitability can increase cell output
This study describes how a progressive inactivation of dendritic Na+ channels during repetitive activity can shift the relation between somatic and dendritic spike timing. A progressive delay in dendritic spike latency increases its effectiveness at generating a depolarizing afterpotential at the soma, leading to a paradoxical increase in somatic spike output in the face of a decrease in dendritic excitability. See Fernandez et al. (2005) PDF

Measurement of stellate first spike latency

A-type K+ and T-type Ca2+ channels generate a novel first spike latency relationship
In this study we examined the mechanism underlying a non-monotonic voltage - first spike latency relationship in cerebellar stellate cells. We show through current and voltage clamp analysis and modeling that A-type and T-type inactivating channels interact to produce a voltage-dependent increase or decrease in first spike latency. The effect depends critically on the voltage-dependence of inactivation and relative density of the respective currents. See Molineux et al. (2005) PDF

The C terminus targets Kv3.3 K+ channels to dendritic regions
This study used viral transfection of Kv3.3 K+ channel constructs to determine the molecular basis for a selective targeting of these channels to dendritic regions of ELL pyramidal cells. We show that dendritic targeting depends on a C-terminal consensus sequence predicted to bind to a PDZ protein-protein interaction motif. By comparison, Kv3.1 channels lack this motif and are restricted to the somatic region.
See Deng et al. (2005) PDF

nckx2 KO animals show a deficit in LTP and motor learning
This study examined the cellular and behavioural roles for the plasma membrane Na+/Ca2+ exchanger-2 using nckx2 knockout animals. nckx2 KO animals exhibit a decrease in calcium influx, a loss of LTP at the Schaefer collateral - CA1 synapse and deficits in specific motor learning and memory tasks. nckx2 effects are not reflected in the membrane or spike output properties of CA1 pyramidal cells, suggesting a potential dendritic or synaptic location of change. See Li et al. (2006) PDF

Firing dynamics of cerebellar Purkinje cells
We show that a simple firing model undergoing a saddle homoclinic bifurcation can reproduce many of the key properties of Purkinje cells. Each spike is followed by a relatively large depolarizing afterpotential (DAP) that can sustain tonic firing given a brief stimulation from rest. Consequently, within the context of a saddle homoclinic bifurcation the DAP is critical for bistable dynamics and many of the other electrophysiological characteristics of Purkinje cells. PDF

Peer-reviewed Publications

Fernandez FR, Morales E, and Turner RW. (2003) Inactivation of Kv3.3 K+ channels in heterologous expression systems. J. Biological Chemistry 278(42): 40890-40898. PDF

Morales E*, Fernandez FR,* Sinclair S, Molineux ML, Mehaffey HW and Turner RW. (2004) Releasing the peri-neuronal net to patch clamp neurons in the adult CNS. Pflugers Archiv 448(2): 248-258. (*shared first author) PDF

Fernandez FR*, Mehaffey WH*, Molineux ML and Turner RW. (2005) High threshold potassium channels increase gain by offsetting a frequency-dependent increase in low threshold potassium current. (*shared first author) J. Neuroscience 25(6): 1481-1492. PDF

Fernandez FR, Mehaffey WH and Turner RW. (2005) Dendritic Na+ current inactivation can increase cell excitability by delaying a somatic depolarizing afterpotential. J. Neurophysiology 94: 3836-3848. PDF

Molineux ML*, Fernandez FR*, Mehaffey WH and Turner RW (2005) A-type and T-type currents interact to produce a novel spike latency-voltage relationship in cerebellar stellate cells. J. Neuroscience 25(47): 10863-10873. (*shared first author). PDF

Deng W, Rashid AJ, Fernandez FR, Maler L, Turner RW and Dunn RJ. (2005) A C-terminal signal directs Kv3.3 channels to dendrites. J. Neuroscience, 25(50): 11531-11541. PDF

Li X-F, Kiedrowski L, Tremblay F, Fernandez FR, Perizzolo M, Winkfein RJ, Turner, RW, Bains JS, Rancourt DE and Lytton J. (2006) Importance of K+-dependent Na+/Ca2+-exchanger 2, NCKX2, in motor learning and memory. J. Biological Chemistry. 281(10): 6273-6282. PDF

Fernandez FR, Engbers JDT and Turner RW. (2007) Firing dynamics of cerebellar Purkinje cells. J. Neurophysiology, 98(1): 278-94. PDF

Mehaffey WH, Fernandez FR, Maler . and Turner RW. (2007) Regulation of burst dynamics improves differential encoding of stimulus frequency by spike train segregation. J. Neurophysiology 98(2): 939-951. PDF

Invited Chapters:
Mehaffey WH*, Fernandez FR*, Rashid AJ, Dunn RJ and Turner RW (2006) The distribution and function of potassium channels in aperonotid electrosensory lateral line lobe. J. Comp. Physiol. A, Neuroethol Sens Neural Behav Physiol. 20:1-12. (*shared first author) PDF

Mehaffey, W.H., Fernandez, F.R., Doiron, B. and Turner, R.W. (2008) Regulation of somatic firing dynamics by backpropagating dendritic spikes. J. Physiol. (Paris) 102: 181-194. PDF

Invited Talks
- 2006 - Dynamics of Purkinje cell bistability, Institute for Theoretical Biology, Humboldt University, Berlin.

Key Abstracts
Morales E, Fernandez FR, Rashid AJ, Dunn RJ and Turner RW. Biophysical properties of apteronotid Kv3.3 and Kv3.1 potassium channels. Proc Soc Neurosci 2002.

Fernandez FR, Mehaffey WH, Rashid AJ, Dunn RJ and Turner RW. Kv3 channel contribution to repetitive spike activity. Proc Soc Neurosci 2003.

Fernandez FR, Mehaffey WH, Molineux ML and Turner RW. High threshold K+ channels increase gain by offsetting a cumulative activation of low threshold K+ current. Proc Soc Neurosci 2004.

Fernandez FR, Mehaffey WH and Turner RW. Dendritic Na+ current inactivation can increase cell excitability by delaying a somatic depolarizing afterpotential. Proc Soc Neurosci 2005.

Fernandez FR and Turner RW. Delay to first firing without A-type K+ currents. Proc Soc Neurosci 2005.

Mehaffey WH, Fernandez FR and Turner RW. Inhibitory GABA-B conductances cause a shift to burst firing mode. Proc Soc Neurosci 2005.

Fernandez FR and Turner RW. Dynamics of first spike latency with and without A-type currents: implications for cerebellar Purkinje cell spike firing dynamics, Comp. Neurosci, 2006.

Fernandez FR and Turner RW. Dynamics of bistability in cerebellar Purkinje cells, Proc Soc Neurosci 2006.

Engbers J.T, Mehaffey WH, Fernandez FR and Turner RW. Synaptic noise modulates the probability of climbing fibre-induced state transitions in cerebellar Purkinje cells. Proc. Soc. Neurosci. 2008.

Engbers, J.D.T., Mehaffey, W.H. Fernandez, F.R. and Turner, R.W. Synaptic noise modulates the probability of climbing fibre-induced state transitions in cerebellar Purkinje cells. Can Assoc. Neurosci. 2009.

Engbers, J.D.T., Mehaffey, W.H. Fernandez, F.R. and Turner, R.W. Synaptic noise modulates the probability of climbing fiber-induced state transitions in cerebellar Purkinje cells. IUPS, Kyoto 2009.

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