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Learning and aging related changes in intrinsic neuronal excitability.

Oh MM, Oliveira FA, Disterhoft JF - Front Aging Neurosci (2010)

Bottom Line: We have consistently found that the postburst AHP is significantly reduced in hippocampal pyramidal neurons from young adults that have successfully learned a hippocampus-dependent task.After understanding the changes, we should be able to formulate strategies for reversing them, thus making old neurons function more as they did when they were young.Such a reversal should rescue the age-related cognitive deficits.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University Chicago, IL, USA.

ABSTRACT
A goal of many laboratories that study aging is to find a key cellular change(s) that can be manipulated and restored to a young-like state, and thus, reverse the age-related cognitive deficits. We have chosen to focus our efforts on the alteration of intrinsic excitability (as reflected by the postburst afterhyperpolarization, AHP) during the learning process in hippocampal pyramidal neurons. We have consistently found that the postburst AHP is significantly reduced in hippocampal pyramidal neurons from young adults that have successfully learned a hippocampus-dependent task. In the context of aging, the baseline intrinsic excitability of hippocampal neurons is decreased and therefore cognitive learning is impaired. In aging animals that are able to learn, neuron changes in excitability similar to those seen in young neurons during learning occur. Our challenge, then, is to understand how and why excitability changes occur in neurons from aging brains and cause age-associated learning impairments. After understanding the changes, we should be able to formulate strategies for reversing them, thus making old neurons function more as they did when they were young. Such a reversal should rescue the age-related cognitive deficits.

No MeSH data available.


Related in: MedlinePlus

Baseline in vivo firing rate of CA1 pyramidal neurons is significantly enhanced with L-type calcium channel blocker nimodipine. (A) Single-unit discrimination (firing neurons) using the spike separation algorithms is illustrated. The top left trace shows 1 s of a typical multi-unit signal recorded midway through stratum pyramidale of field CAl in the dorsal hippocampus with clear theta frequency (4–8 Hz) modulation of the firing of many cells. The lower left trace shows 5 s of a classic “single-unit” signal (pyramidal neuron) recorded in the same rabbit. Simple window discrimination of this “unitary” signal (possessing fairly uniform peak-to-peak spike amplitude) would yield a frequency estimation of 2.0 ± 0.3 Hz. (B) Intravenous infusion of nimodipine significantly increased the spontaneous activity of CA1 pyramidal neurons (filled circles) while reducing the spontaneous activity of theta (interneuron) cells (open box) recorded from the dorsal hippocampus of aging rabbits. Reprinted with permission from Thompson et al. (1990) © Elsevier Science Publishers B. V. (Biomedical Division).
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Figure 2: Baseline in vivo firing rate of CA1 pyramidal neurons is significantly enhanced with L-type calcium channel blocker nimodipine. (A) Single-unit discrimination (firing neurons) using the spike separation algorithms is illustrated. The top left trace shows 1 s of a typical multi-unit signal recorded midway through stratum pyramidale of field CAl in the dorsal hippocampus with clear theta frequency (4–8 Hz) modulation of the firing of many cells. The lower left trace shows 5 s of a classic “single-unit” signal (pyramidal neuron) recorded in the same rabbit. Simple window discrimination of this “unitary” signal (possessing fairly uniform peak-to-peak spike amplitude) would yield a frequency estimation of 2.0 ± 0.3 Hz. (B) Intravenous infusion of nimodipine significantly increased the spontaneous activity of CA1 pyramidal neurons (filled circles) while reducing the spontaneous activity of theta (interneuron) cells (open box) recorded from the dorsal hippocampus of aging rabbits. Reprinted with permission from Thompson et al. (1990) © Elsevier Science Publishers B. V. (Biomedical Division).

Mentions: In addition to the learning-related alterations in firing rate in vivo, the basal firing rate of CA1 pyramidal neurons may be directly correlated with the postburst AHP. As stated previously, there are two distinct populations in the aging group: those that are able to successfully learn and those that fail (Thompson et al., 1996b; Knuttinen et al., 2001; Tombaugh et al., 2005). Notably, aging animals that are able to learn have postburst AHPs that are similar to that observed in young adults (Moyer et al., 2000; Tombaugh et al., 2005) and have in vivo basal firing rates that are also similar to that observed in young adults (McEchron et al., 2001). Those aging animals that fail to learn have significantly larger postburst AHPs (Moyer et al., 2000; Tombaugh et al., 2005) and have significantly lower in vivo basal firing rates than young adults (McEchron et al., 2001). However, the in vivo basal firing rate of CA1 neurons from aging animals can be elevated by pharmacological compounds that also reduce the postburst AHP in vitro and ameliorate the age-related learning impairments (Thompson et al., 1990) (Figure 2). Therefore, modulation of intrinsic neuronal excitability of hippocampal pyramidal neurons has a direct impact on the neuronal network activity.


Learning and aging related changes in intrinsic neuronal excitability.

Oh MM, Oliveira FA, Disterhoft JF - Front Aging Neurosci (2010)

Baseline in vivo firing rate of CA1 pyramidal neurons is significantly enhanced with L-type calcium channel blocker nimodipine. (A) Single-unit discrimination (firing neurons) using the spike separation algorithms is illustrated. The top left trace shows 1 s of a typical multi-unit signal recorded midway through stratum pyramidale of field CAl in the dorsal hippocampus with clear theta frequency (4–8 Hz) modulation of the firing of many cells. The lower left trace shows 5 s of a classic “single-unit” signal (pyramidal neuron) recorded in the same rabbit. Simple window discrimination of this “unitary” signal (possessing fairly uniform peak-to-peak spike amplitude) would yield a frequency estimation of 2.0 ± 0.3 Hz. (B) Intravenous infusion of nimodipine significantly increased the spontaneous activity of CA1 pyramidal neurons (filled circles) while reducing the spontaneous activity of theta (interneuron) cells (open box) recorded from the dorsal hippocampus of aging rabbits. Reprinted with permission from Thompson et al. (1990) © Elsevier Science Publishers B. V. (Biomedical Division).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2874400&req=5

Figure 2: Baseline in vivo firing rate of CA1 pyramidal neurons is significantly enhanced with L-type calcium channel blocker nimodipine. (A) Single-unit discrimination (firing neurons) using the spike separation algorithms is illustrated. The top left trace shows 1 s of a typical multi-unit signal recorded midway through stratum pyramidale of field CAl in the dorsal hippocampus with clear theta frequency (4–8 Hz) modulation of the firing of many cells. The lower left trace shows 5 s of a classic “single-unit” signal (pyramidal neuron) recorded in the same rabbit. Simple window discrimination of this “unitary” signal (possessing fairly uniform peak-to-peak spike amplitude) would yield a frequency estimation of 2.0 ± 0.3 Hz. (B) Intravenous infusion of nimodipine significantly increased the spontaneous activity of CA1 pyramidal neurons (filled circles) while reducing the spontaneous activity of theta (interneuron) cells (open box) recorded from the dorsal hippocampus of aging rabbits. Reprinted with permission from Thompson et al. (1990) © Elsevier Science Publishers B. V. (Biomedical Division).
Mentions: In addition to the learning-related alterations in firing rate in vivo, the basal firing rate of CA1 pyramidal neurons may be directly correlated with the postburst AHP. As stated previously, there are two distinct populations in the aging group: those that are able to successfully learn and those that fail (Thompson et al., 1996b; Knuttinen et al., 2001; Tombaugh et al., 2005). Notably, aging animals that are able to learn have postburst AHPs that are similar to that observed in young adults (Moyer et al., 2000; Tombaugh et al., 2005) and have in vivo basal firing rates that are also similar to that observed in young adults (McEchron et al., 2001). Those aging animals that fail to learn have significantly larger postburst AHPs (Moyer et al., 2000; Tombaugh et al., 2005) and have significantly lower in vivo basal firing rates than young adults (McEchron et al., 2001). However, the in vivo basal firing rate of CA1 neurons from aging animals can be elevated by pharmacological compounds that also reduce the postburst AHP in vitro and ameliorate the age-related learning impairments (Thompson et al., 1990) (Figure 2). Therefore, modulation of intrinsic neuronal excitability of hippocampal pyramidal neurons has a direct impact on the neuronal network activity.

Bottom Line: We have consistently found that the postburst AHP is significantly reduced in hippocampal pyramidal neurons from young adults that have successfully learned a hippocampus-dependent task.After understanding the changes, we should be able to formulate strategies for reversing them, thus making old neurons function more as they did when they were young.Such a reversal should rescue the age-related cognitive deficits.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University Chicago, IL, USA.

ABSTRACT
A goal of many laboratories that study aging is to find a key cellular change(s) that can be manipulated and restored to a young-like state, and thus, reverse the age-related cognitive deficits. We have chosen to focus our efforts on the alteration of intrinsic excitability (as reflected by the postburst afterhyperpolarization, AHP) during the learning process in hippocampal pyramidal neurons. We have consistently found that the postburst AHP is significantly reduced in hippocampal pyramidal neurons from young adults that have successfully learned a hippocampus-dependent task. In the context of aging, the baseline intrinsic excitability of hippocampal neurons is decreased and therefore cognitive learning is impaired. In aging animals that are able to learn, neuron changes in excitability similar to those seen in young neurons during learning occur. Our challenge, then, is to understand how and why excitability changes occur in neurons from aging brains and cause age-associated learning impairments. After understanding the changes, we should be able to formulate strategies for reversing them, thus making old neurons function more as they did when they were young. Such a reversal should rescue the age-related cognitive deficits.

No MeSH data available.


Related in: MedlinePlus