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T-type calcium channels cause bursts of spikes in motor but not sensory thalamic neurons during mimicry of natural patterns of synaptic input

View Article: PubMed Central

ABSTRACT

Although neurons within intact nervous systems can be classified as ‘sensory’ or ‘motor,’ it is not known whether there is any general distinction between sensory and motor neurons at the cellular or molecular levels. Here, we extend and test a theory according to which activation of certain subtypes of voltage-gated ion channel (VGC) generate patterns of spikes in neurons of motor systems, whereas VGC are proposed to counteract patterns in sensory neurons. We previously reported experimental evidence for the theory from visual thalamus, where we found that T-type calcium channels (TtCCs) did not cause bursts of spikes but instead served the function of ‘predictive homeostasis’ to maximize the causal and informational link between retinogeniculate excitation and spike output. Here, we have recorded neurons in brain slices from eight sensory and motor regions of rat thalamus while mimicking key features of natural excitatory and inhibitory post-synaptic potentials. As predicted by theory, TtCC did cause bursts of spikes in motor thalamus. TtCC-mediated responses in motor thalamus were activated at more hyperpolarized potentials and caused larger depolarizations with more spikes than in visual and auditory thalamus. Somatosensory thalamus is known to be more closely connected to motor regions relative to auditory and visual thalamus, and likewise the strength of its TtCC responses was intermediate between these regions and motor thalamus. We also observed lower input resistance, as well as limited evidence of stronger hyperpolarization-induced (‘H-type’) depolarization, in nuclei closer to motor output. These findings support our theory of a specific difference between sensory and motor neurons at the cellular level.

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Population average T-type depolarization is larger in motor than visual thalamus. (A) TtD (mean ± SEM) in VL (black) and LGN (red) in the DCSW protocol. The current was selected in each cell that caused an initial depolarization (at current offset) nearest to 11.3 mV (the smallest depolarization present in all cells; range: 9.6–11.9 mV) when injected after 50 ms near -80 mV. Raw voltage responses are shown at top and isolated TtD at bottom (found by subtracting responses at 50 ms in each cell prior to averaging). Fewer cells were tested at 100 ms (Table 2). (B) Analogous to (A) but for the CCSW protocol. Initial depolarizations were selected to be nearly the same across all neurons but differed across the three baseline voltages. (C) Population average responses just below (top) and above threshold (bottom) for generation of sodium spikes. Neurons were discarded if no spikes were evoked by any current, and thus more neurons were discarded at earlier times. Similar differences between VL and LGN were apparent when analysis was restricted to neurons tested up to 1000 pA (which caused a spike in all neurons at all times). (D) The fLTS evoked from near -80 mV in the presence of TTX (0.5–2.0 μM) in all 30 neurons in which it was administered, including eight and seven neurons in DCSW (800 ms) and CCSW protocols, respectively, in both VL (left) and LGN (right). (E) For the neurons in (D) the population fLTS (mean ± SEM; left), the LTS in response to 100 pA more than required to evoke the fLTS (middle), and the LTS in response to our maximum tested current of 1000 pA (right; 1000 pA was tested in only 14 neurons, seven in VL and LGN, in the DCSW protocol). The fLTS was evoked by currents of 180–660 pA across all neurons. The timing of the LTS was less variable in response to larger currents, and this allows the sharp initial peak to appear in the population average with 1000 pA (right) but not smaller currents (left and middle).
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Figure 3: Population average T-type depolarization is larger in motor than visual thalamus. (A) TtD (mean ± SEM) in VL (black) and LGN (red) in the DCSW protocol. The current was selected in each cell that caused an initial depolarization (at current offset) nearest to 11.3 mV (the smallest depolarization present in all cells; range: 9.6–11.9 mV) when injected after 50 ms near -80 mV. Raw voltage responses are shown at top and isolated TtD at bottom (found by subtracting responses at 50 ms in each cell prior to averaging). Fewer cells were tested at 100 ms (Table 2). (B) Analogous to (A) but for the CCSW protocol. Initial depolarizations were selected to be nearly the same across all neurons but differed across the three baseline voltages. (C) Population average responses just below (top) and above threshold (bottom) for generation of sodium spikes. Neurons were discarded if no spikes were evoked by any current, and thus more neurons were discarded at earlier times. Similar differences between VL and LGN were apparent when analysis was restricted to neurons tested up to 1000 pA (which caused a spike in all neurons at all times). (D) The fLTS evoked from near -80 mV in the presence of TTX (0.5–2.0 μM) in all 30 neurons in which it was administered, including eight and seven neurons in DCSW (800 ms) and CCSW protocols, respectively, in both VL (left) and LGN (right). (E) For the neurons in (D) the population fLTS (mean ± SEM; left), the LTS in response to 100 pA more than required to evoke the fLTS (middle), and the LTS in response to our maximum tested current of 1000 pA (right; 1000 pA was tested in only 14 neurons, seven in VL and LGN, in the DCSW protocol). The fLTS was evoked by currents of 180–660 pA across all neurons. The timing of the LTS was less variable in response to larger currents, and this allows the sharp initial peak to appear in the population average with 1000 pA (right) but not smaller currents (left and middle).

Mentions: Differences between motor and visual thalamus can also be seen in population average voltage responses (Figure 3). In response to nearly equal initial depolarizations, the average TtD was larger in VL than LGN after 200 ms and more near -80 mV (Figure 3A) in the DCSW protocol and from all holding potentials in the CCSW protocol (-70, -80, and -90 mV; Figure 3B). Subthreshold responses were smaller and super-threshold responses were larger in VL (Figure 3C, compare top and bottom), suggesting that TtCC activation had more all-or-none character in VL and was more graded in LGN.


T-type calcium channels cause bursts of spikes in motor but not sensory thalamic neurons during mimicry of natural patterns of synaptic input
Population average T-type depolarization is larger in motor than visual thalamus. (A) TtD (mean ± SEM) in VL (black) and LGN (red) in the DCSW protocol. The current was selected in each cell that caused an initial depolarization (at current offset) nearest to 11.3 mV (the smallest depolarization present in all cells; range: 9.6–11.9 mV) when injected after 50 ms near -80 mV. Raw voltage responses are shown at top and isolated TtD at bottom (found by subtracting responses at 50 ms in each cell prior to averaging). Fewer cells were tested at 100 ms (Table 2). (B) Analogous to (A) but for the CCSW protocol. Initial depolarizations were selected to be nearly the same across all neurons but differed across the three baseline voltages. (C) Population average responses just below (top) and above threshold (bottom) for generation of sodium spikes. Neurons were discarded if no spikes were evoked by any current, and thus more neurons were discarded at earlier times. Similar differences between VL and LGN were apparent when analysis was restricted to neurons tested up to 1000 pA (which caused a spike in all neurons at all times). (D) The fLTS evoked from near -80 mV in the presence of TTX (0.5–2.0 μM) in all 30 neurons in which it was administered, including eight and seven neurons in DCSW (800 ms) and CCSW protocols, respectively, in both VL (left) and LGN (right). (E) For the neurons in (D) the population fLTS (mean ± SEM; left), the LTS in response to 100 pA more than required to evoke the fLTS (middle), and the LTS in response to our maximum tested current of 1000 pA (right; 1000 pA was tested in only 14 neurons, seven in VL and LGN, in the DCSW protocol). The fLTS was evoked by currents of 180–660 pA across all neurons. The timing of the LTS was less variable in response to larger currents, and this allows the sharp initial peak to appear in the population average with 1000 pA (right) but not smaller currents (left and middle).
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Related In: Results  -  Collection

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Figure 3: Population average T-type depolarization is larger in motor than visual thalamus. (A) TtD (mean ± SEM) in VL (black) and LGN (red) in the DCSW protocol. The current was selected in each cell that caused an initial depolarization (at current offset) nearest to 11.3 mV (the smallest depolarization present in all cells; range: 9.6–11.9 mV) when injected after 50 ms near -80 mV. Raw voltage responses are shown at top and isolated TtD at bottom (found by subtracting responses at 50 ms in each cell prior to averaging). Fewer cells were tested at 100 ms (Table 2). (B) Analogous to (A) but for the CCSW protocol. Initial depolarizations were selected to be nearly the same across all neurons but differed across the three baseline voltages. (C) Population average responses just below (top) and above threshold (bottom) for generation of sodium spikes. Neurons were discarded if no spikes were evoked by any current, and thus more neurons were discarded at earlier times. Similar differences between VL and LGN were apparent when analysis was restricted to neurons tested up to 1000 pA (which caused a spike in all neurons at all times). (D) The fLTS evoked from near -80 mV in the presence of TTX (0.5–2.0 μM) in all 30 neurons in which it was administered, including eight and seven neurons in DCSW (800 ms) and CCSW protocols, respectively, in both VL (left) and LGN (right). (E) For the neurons in (D) the population fLTS (mean ± SEM; left), the LTS in response to 100 pA more than required to evoke the fLTS (middle), and the LTS in response to our maximum tested current of 1000 pA (right; 1000 pA was tested in only 14 neurons, seven in VL and LGN, in the DCSW protocol). The fLTS was evoked by currents of 180–660 pA across all neurons. The timing of the LTS was less variable in response to larger currents, and this allows the sharp initial peak to appear in the population average with 1000 pA (right) but not smaller currents (left and middle).
Mentions: Differences between motor and visual thalamus can also be seen in population average voltage responses (Figure 3). In response to nearly equal initial depolarizations, the average TtD was larger in VL than LGN after 200 ms and more near -80 mV (Figure 3A) in the DCSW protocol and from all holding potentials in the CCSW protocol (-70, -80, and -90 mV; Figure 3B). Subthreshold responses were smaller and super-threshold responses were larger in VL (Figure 3C, compare top and bottom), suggesting that TtCC activation had more all-or-none character in VL and was more graded in LGN.

View Article: PubMed Central

ABSTRACT

Although neurons within intact nervous systems can be classified as ‘sensory’ or ‘motor,’ it is not known whether there is any general distinction between sensory and motor neurons at the cellular or molecular levels. Here, we extend and test a theory according to which activation of certain subtypes of voltage-gated ion channel (VGC) generate patterns of spikes in neurons of motor systems, whereas VGC are proposed to counteract patterns in sensory neurons. We previously reported experimental evidence for the theory from visual thalamus, where we found that T-type calcium channels (TtCCs) did not cause bursts of spikes but instead served the function of ‘predictive homeostasis’ to maximize the causal and informational link between retinogeniculate excitation and spike output. Here, we have recorded neurons in brain slices from eight sensory and motor regions of rat thalamus while mimicking key features of natural excitatory and inhibitory post-synaptic potentials. As predicted by theory, TtCC did cause bursts of spikes in motor thalamus. TtCC-mediated responses in motor thalamus were activated at more hyperpolarized potentials and caused larger depolarizations with more spikes than in visual and auditory thalamus. Somatosensory thalamus is known to be more closely connected to motor regions relative to auditory and visual thalamus, and likewise the strength of its TtCC responses was intermediate between these regions and motor thalamus. We also observed lower input resistance, as well as limited evidence of stronger hyperpolarization-induced (‘H-type’) depolarization, in nuclei closer to motor output. These findings support our theory of a specific difference between sensory and motor neurons at the cellular level.

No MeSH data available.


Related in: MedlinePlus