Decision letter: Target-specific membrane potential dynamics of neocortical projection neurons during goal-directed behavior

Goal-directed behavior involves distributed neuronal circuits in the mammalian brain, including diverse regions of neocortex. However, the cellular basis of long-range cortico-cortical signaling during goal-directed behavior is poorly understood. Here, we recorded membrane potential of excitatory layer 2/3 pyramidal neurons in primary somatosensory barrel cortex (S1) projecting to either primary motor cortex (M1) or secondary somatosensory cortex (S2) during a whisker detection task, in which thirsty mice learn to lick for water reward in response to a whisker deflection. Whisker stimulation in ‘Good performer’ mice, but not ‘Naive’ mice, evoked long-lasting biphasic depolarization correlated with task performance in S2-projecting (S2-p) neurons, but not M1-projecting (M1-p) neurons. Furthermore, S2-p neurons, but not M1-p neurons, became excited during spontaneous unrewarded licking in ‘Good performer’ mice, but not in ‘Naive’ mice. Thus, a learning-induced, projection-specific signal from S1 to S2 may contribute to goal-directed sensorimotor transformation of whisker sensation into licking motor output.

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Membrane Potential Dynamics of Neocortical Projection Neurons Driving Target-Specific Signals

Neuron ◽

10.1016/j.neuron.2013.10.059 ◽

2013 ◽

Vol 80 (6) ◽

pp. 1477-1490 ◽

Cited By ~ 101

Author(s):

Takayuki Yamashita ◽

Aurélie Pala ◽

Leticia Pedrido ◽

Yves Kremer ◽

Egbert Welker ◽

...

Keyword(s):

Membrane Potential ◽

Projection Neurons

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Mapping Membrane Potential Transients in Crayfish (Procambarus clarkii) Optic Lobe Neuropils With Voltage-Sensitive Dyes

Journal of Neurophysiology ◽

10.1152/jn.1999.81.1.334 ◽

1999 ◽

Vol 81 (1) ◽

pp. 334-344 ◽

Cited By ~ 6

Author(s):

Sergey Yagodin ◽

Carlos Collin ◽

Daniel L. Alkon ◽

Norman F. Sheppard ◽

David B. Sattelle

Keyword(s):

Membrane Potential ◽

Visual Information ◽

Action Potentials ◽

Optic Lobe ◽

Procambarus Clarkii ◽

Projection Neurons ◽

Medulla Terminalis ◽

Voltage Sensitive Dyes ◽

Hemiellipsoid Body ◽

Synaptic Responses

Yagodin, Sergey, Carlos Collin, Daniel L. Alkon, Norman F. Sheppard, Jr., and David B. Sattelle. Mapping membrane potential transients in crayfish ( Procambarus clarkii) optic lobe neuropils with voltage-sensitive dyes. J. Neurophysiol. 81: 334–344, 1999. Voltage-sensitive dyes NK 2761 and RH 155 were employed (in conjunction with a 12 × 12 photodiode array) to study membrane potential transients in optic lobe neuropils in the eye stalk of the crayfish Procambarus clarkii. By this means we investigated a pathway linking deutocerebral projection neurons, via hemiellipsoid body local interneurons, to an unidentified target (most likely neurons processing visual information) in the medulla terminalis. Rapid (10- to 20-ms duration), transient changes in absorption with the characteristics of action potentials were recorded from the optic nerve and the region occupied by deutocerebral projection neurons after stimulation of the olfactory globular tract in the optic nerve and were blocked by 1 μM tetrodotoxin. Action potentials appeared to propagate to the glomerular layer of the hemiellipsoid body where synaptic responses were recorded from a restricted region of the hemiellipsoid body occupied by dendrites of hemiellipsoid body neurons. Action potentials were also recorded from processes of hemiellipsoid body neurons located in the medulla terminalis. Synaptic responses in the hemiellipsoid body and medulla terminalis were eliminated by addition to the saline of 500 μM Cd2+ or 20 mM Co2+, whereas the action potential attributed to branches of deutocerebral projection neurons in the hemiellipsoid body remained unaffected. Action potentials of hemiellipsoid body neurons in the medulla terminalis evoked postsynaptic potentials (50- to 200-ms duration) with an unidentified target in the medulla terminalis. Transient absorption signals were not detected in either the internal or external medulla nor were they recorded from other parts of the optic lobes in response to electrical stimulation of axons of the deutocerebral projection neurons. Functional maps of optical activity, together with electrophysiological and pharmacological findings, suggest that γ-aminobutyric acid affects synaptic transmission in glomeruli of the hemiellipsoid body. Synapses of the olfactory pathway located in the medulla terminalis may act as a “filter,” modifying visual information processing during olfactory stimulation.

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Differential electroresponsiveness of stellate and pyramidal-like cells of medial entorhinal cortex layer II

Journal of Neurophysiology ◽

10.1152/jn.1993.70.1.128 ◽

1993 ◽

Vol 70 (1) ◽

pp. 128-143 ◽

Cited By ~ 279

Author(s):

A. Alonso ◽

R. Klink

Keyword(s):

Membrane Potential ◽

Entorhinal Cortex ◽

Morphological Characteristics ◽

Oscillatory Activity ◽

Inward Rectification ◽

Projection Neurons ◽

Medial Entorhinal Cortex ◽

Mean Frequency ◽

Subthreshold Oscillations

1. The electroresponsive properties of neurons from layer II of the rat medial entorhinal cortex (MEC) were studied by intracellular recording under current clamp in an in vitro brain slice preparation. From a total of 184 cells that fulfilled our criteria for recording stability, two groups of projection neurons were distinguished on the basis of their intrinsic biophysical properties and morphological characteristics (demonstrated by intracellular biocytin injection; n = 34). 2. Stellate cells (SCs) were the most abundant (69%). They were highly electroresponsive, and minimal changes (1-3 mV) of membrane potential generated an active response. Subthreshold depolarizing or hyperpolarizing current pulse injection always caused the membrane potential to attain an early peak and then sag to a lower level. Depolarization-induced "sags" were larger and determined early firing in all cells. The voltage-current relationship of SCs was markedly non-linear, demonstrating robust inward rectification in the hyperpolarizing and depolarizing range. 3. SCs generated persistent rhythmic subthreshold voltage oscillations on DC depolarization positive to -60 mV. The mean frequency of the oscillations was 8.6 Hz (theta range) at a membrane potential of approximately -55 mV, at which level occasional single spiking also occurred. At slightly more positive potentials, a striking 1- to 3-Hz repetitive bursting pattern emerged. This consisted of nonadapting trains of spikes ("clusters") interspersed with subthreshold oscillations that had a mean frequency of 21.7 Hz (beta range). 4. Nonstellate cells (39%; mostly pyramidal-like) displayed time-dependent inward rectification that was less pronounced than that of SCs, and minimal depolarization-induced sags. On threshold depolarization, firing was always preceded by a slowly rising ramp depolarization and thus occurred with a long delay. Inward rectification in the depolarizing range was very pronounced. However, non-SCs did not generate persistent rhythmic subthreshold oscillatory activity or spike clusters. 5. Of the electrophysiological parameters quantified, spike threshold, spike duration, depolarizing afterpotential amplitude and apparent membrane time constant demonstrated statistically significant differences between SCs and non-SCs. 6. The repetitive hiring properties in response to square current pulses of short duration (< 500 ms) were also different between SCs and non-SCs. First, most SCs displayed a bilinear frequency-current (f-I) relationship for only the first interspike interval, whereas most non-SCs displayed a bilinear relationship for all intervals. Second, SCs had a much steeper primary f-I slope for early intervals than non-SCs. Finally, SCs displayed more pronounced and faster spike frequency adaptation than non-SCs.(ABSTRACT TRUNCATED AT 400 WORDS)

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Cell-Type-Specific Sensorimotor Processing in Striatal Projection Neurons during Goal-Directed Behavior

Neuron ◽

10.1016/j.neuron.2015.08.039 ◽

2015 ◽

Vol 88 (2) ◽

pp. 298-305 ◽

Cited By ~ 97

Author(s):

Tanya Sippy ◽

Damien Lapray ◽

Sylvain Crochet ◽

Carl C.H. Petersen

Keyword(s):

Projection Neurons ◽

Cell Type ◽

Sensorimotor Processing ◽

Striatal Projection Neurons ◽

Cell Type Specific ◽

Goal Directed Behavior

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Pauses in cholinergic interneuron firing exert an inhibitory control on striatal output in vivo

eLife ◽

10.7554/elife.32510 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 15

Author(s):

Stefano Zucca ◽

Aya Zucca ◽

Takashi Nakano ◽

Sho Aoki ◽

Jeffery Wickens

Keyword(s):

Membrane Potential ◽

Projection Neurons ◽

Tonic Firing ◽

Short Term Plasticity ◽

Cholinergic Interneurons ◽

Significant Events ◽

Output Neurons ◽

Potential Activity ◽

Membrane Potential Fluctuations

The cholinergic interneurons (CINs) of the striatum are crucial for normal motor and behavioral functions of the basal ganglia. Striatal CINs exhibit tonic firing punctuated by distinct pauses. Pauses occur in response to motivationally significant events, but their function is unknown. Here we investigated the effects of pauses in CIN firing on spiny projection neurons (SPNs) – the output neurons of the striatum – using in vivo whole cell and juxtacellular recordings in mice. We found that optogenetically-induced pauses in CIN firing inhibited subthreshold membrane potential activity and decreased firing of SPNs. During pauses, SPN membrane potential fluctuations became more hyperpolarized and UP state durations became shorter. In addition, short-term plasticity of corticostriatal inputs was decreased during pauses. Our results indicate that, in vivo, the net effect of the pause in CIN firing on SPNs activity is inhibition and provide a novel mechanism for cholinergic control of striatal output.

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Properties and physiological function of Ca2+-dependent K+ currents in uniglomerular olfactory projection neurons

Journal of Neurophysiology ◽

10.1152/jn.00840.2015 ◽

2016 ◽

Vol 115 (5) ◽

pp. 2330-2340 ◽

Cited By ~ 2

Author(s):

Cathleen Bradler ◽

Ben Warren ◽

Viktor Bardos ◽

Sabine Schleicher ◽

Andreas Klein ◽

...

Keyword(s):

Membrane Potential ◽

Intracellular Signaling ◽

Periplaneta Americana ◽

Bk Channels ◽

Adult Brain ◽

Insect Brain ◽

Projection Neurons ◽

Membrane Excitability ◽

Electrophysiological Properties ◽

Ionic Mechanisms

Ca2+-activated potassium currents [ IK(Ca)] are an important link between the intracellular signaling system and the membrane potential, which shapes intrinsic electrophysiological properties. To better understand the ionic mechanisms that mediate intrinsic firing properties of olfactory uniglomerular projection neurons (uPNs), we used whole cell patch-clamp recordings in an intact adult brain preparation of the male cockroach Periplaneta americana to analyze IK(Ca). In the insect brain, uPNs form the principal pathway from the antennal lobe to the protocerebrum, where centers for multimodal sensory processing and learning are located. In uPNs the activation of IK(Ca) was clearly voltage and Ca2+ dependent. Thus under physiological conditions IK(Ca) is strongly dependent on Ca2+ influx kinetics and on the membrane potential. The biophysical characterization suggests that IK(Ca) is generated by big-conductance (BK) channels. A small-conductance (SK) channel-generated current could not be detected. IK(Ca) was sensitive to charybdotoxin (CTX) and iberiotoxin (IbTX) but not to apamin. The functional role of IK(Ca) was analyzed in occlusion experiments under current clamp, in which portions of IK(Ca) were blocked by CTX or IbTX. Blockade of IK(Ca) showed that IK(Ca) contributes significantly to intrinsic electrophysiological properties such as the action potential waveform and membrane excitability.

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Cell type-specific membrane potential changes in dorsolateral striatum accompanying reward-based sensorimotor learning

Function ◽

10.1093/function/zqab049 ◽

2021 ◽

Author(s):

Tanya Sippy ◽

Corryn Chaimowitz ◽

Sylvain Crochet ◽

Carl C H Petersen

Keyword(s):

Membrane Potential ◽

Dopamine Receptors ◽

Cell Types ◽

Projection Neurons ◽

Striatal Neurons ◽

Cell Type ◽

Indirect Pathway ◽

Cell Type Specific ◽

Striatal Membrane ◽

Sensory Evoked

Abstract The striatum integrates sensorimotor and motivational signals, likely playing a key role in reward-based learning of goal-directed behavior. However, cell type-specific mechanisms underlying reinforcement learning remain to be precisely determined. Here, we investigated changes in membrane potential dynamics of dorsolateral striatal neurons comparing naïve mice and expert mice trained to lick a reward spout in response to whisker deflection. We recorded from three distinct cell types: i) direct pathway striatonigral neurons, which express type 1 dopamine receptors; ii) indirect pathway striatopallidal neurons, which express type 2 dopamine receptors; and iii) tonically active, putative cholinergic, striatal neurons. Task learning was accompanied by cell type-specific changes in the membrane potential dynamics evoked by the whisker deflection and licking in successfully-performed trials. Both striatonigral and striatopallidal types of striatal projection neurons showed enhanced task-related depolarization across learning. Striatonigral neurons showed a prominent increase in a short latency sensory-evoked depolarization in expert compared to naïve mice. In contrast, the putative cholinergic striatal neurons developed a hyperpolarizing response across learning, driving a pause in their firing. Our results reveal cell type-specific changes in striatal membrane potential dynamics across the learning of a simple goal-directed sensorimotor transformation, helpful for furthering the understanding of the various potential roles of different basal ganglia circuits.

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A single-cell technique for the measurement of membrane potential, membrane conductance, and the efflux of rapidly penetrating solutes in Amphiuma erythrocytes.

The Journal of General Physiology ◽

10.1085/jgp.76.4.455 ◽

1980 ◽

Vol 76 (4) ◽

pp. 455-478 ◽

Cited By ~ 6

Author(s):

L C Stoner ◽

F M Kregenow

Keyword(s):

Membrane Potential ◽

Single Cell ◽

Anion Exchange ◽

Blood Cells ◽

Membrane Surface ◽

Membrane Conductance ◽

Membrane Resistance ◽

Disulfonic Acid ◽

Specific Membrane ◽

Total Membrane

We describe a single-cell technique for measuring membrane potential, membrane resistance, and the efflux of rapidly penetrating solutes such as Cl and H2O. Erythrocytes from Amphiuma means were aspirated into a Sylgard (Dow Corning Corp.)-coated capillary. The aspirated cell separated a solution within the capillary from a solution in the bath. Each of these two solutions was contiguous with approximately 5% of the total membrane surface. Microelectrodes placed concentrically within the capillary permit the measurement of intracellular voltage, specific membrane resistance, and the electrical seal between the two solutions. The intracellular voltage averaged -17.7 mV (pH 7.6) and changed as either intra- or extracellular chloride was varied. The average specific membrane resistance measured by passing current across the exposed membrane surface was 110 ohm-cm2. 36Cl and tritiated H2O fluxes (0.84 +/- 0.05 x 10(-6) M . cm-2 . min-1 and 6.4 +/- 1.5 x 10(-3) M . cm-2 . min-1, respectively) were determined by noting the rate at which isotope leaves the cell and crosses the membrane exposed to the bath. Our measured values for the flux of 36Cl and tritiated H2O approximate reported values for free-floating cells. 36Cl efflux, in addition, is inhibited by 4-acetamido-4'-isothiocyano-stilbene 2,2'-disulfonic acid (SITS) and furosemide, known inhibitors of the anion exchange mechanism responsible for the rapid anion fluxes of red blood cells. One can also demonstrate directly that > 89% of 36Cl efflux is "electrically silent" by analyzing the flux in the presence of an imposed transcellular voltage.

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