Time-lapse electrical recordings of single neurons from the mouse neocortex

Abstract

The ability of the brain to adapt to environmental demands implies that neurons can change throughout life. The extent to which single neurons actually change remains largely unstudied, however. To evaluate how functional properties of single neurons change over time, we devised a way to perform in vivo time-lapse electrophysiological recordings from the exact same neuron. We monitored the contralateral and ipsilateral sensory-evoked spiking activity of individual L2/3 neurons from the somatosensory cortex of mice. At the end of the first recording session, we electroporated the neuron with a DNA plasmid to drive GFP expression. Then, 2 wk later, we visually guided a recording electrode in vivo to the GFP-expressing neuron for the second time. We found that contralateral and ipsilateral evoked responses (i.e., probability to respond, latency, and preference), and spontaneous activity of individual L2/3 pyramidal neurons are stable under control conditions, but that this stability could be rapidly disrupted. Contralateral whisker deprivation induced robust changes in sensoryevoked response profiles of single neurons. Our experiments provide a framework for studying the stability and plasticity of single neurons over long time scales using electrophysiology.electroporation | two-photon imaging I t is well established that the morphology and response properties of neurons are highly dynamic during development. Immature cortical neurons are particularly amenable to change during specific stages of development, when spontaneous activity and sensory experience shape their morphology and physiology (1-4). Once formed and stabilized, neurons are thought to maintain some aspects of this plasticity during adulthood, albeit at a lower level (5-7); however, the extent to which single-neuron physiology changes or remains stable in the adult mammalian brain is poorly documented.Limitations to the study of single-neuron plasticity stem from technical difficulties as well as from the inherent heterogeneity of single neurons in a circuit. Fine changes, like those that underlie functional plasticity, can go undetected due to data averaging and homeostatic events that may cancel out each other. As a result, plasticity is made experimentally more tractable by studying populations after gross manipulations like sensory deprivation or injury. For example, receptive fields of neurons across adult rodent cortices are known to shift in response to different paradigms of sensory input manipulation (8-14). Whether and how other forms of plasticity, such as learning and memory, mark their signature on single neurons is more difficult to deduce from gross manipulation studies. One way to overcome some of these difficulties is through experiments based on time-lapse imaging and electrophysiology (14-18). However, the ability to measure fine temporal physiological events of identifiable single neurons over long time scales remains limited, especially with electrophysiology.To establish a method to follow the electrophysiology of single neuron...

Cortical fosGFP Expression Reveals Broad Receptive Field Excitatory Neurons Targeted by POm

“…While levels of fosGFP are likely to change over the lifetime of a mouse, recent studies show that firing rates in individual cortical neurons can be stable over weeks (Cohen et al, 2013;Margolis et al, 2012). Therefore, fosGFP + neurons could be a stable population of neurons that overlaps with multi-whisker-responsive cortical neurons identified using other techniques (Estebanez et al, 2012;Ghazanfar and Nicolelis, 1997;Sato and Svoboda, 2010).…”

Variance and invariance of neuronal long-term representations

“…[17,18]). Only recent years have seen a prominent increase in the number of mostly imaging studies addressing the stability and plasticity of neuronal representations in the visual system [15,19,35,36,38,41,43,44,46], barrel cortex [14,29,39,47,60] and auditory cortex [42]. …”

“…Later studies, however, showed less variable evoked activity in slightly different paradigms. Using single-cell electrophysiological recordings, preference for ipsi- or contralateral whisker stimulation was shown to be stable over 14 days in the small number of cells tested [60]. While confirming a certain degree of session-to-session variability, later Ca 2+ imaging data also showed that some representations in S1 are largely drift-free because the performance of a population decoder of whisker deflection frequency did not progressively decline when trained on an early session and applied to later sessions [47].…”

“…All these factors are likely to directly affect the assessment of neuronal variability. Furthermore, longitudinal recordings of cellular activity have been performed using a plethora of different experimental paradigms in multiple preparations—from in vitro recordings in dissociated cultures [58,59] to in vivo recordings in primary and higher sensory areas [14,15,18,19,29,35,36,38,39,41–44,46,47,49,60], motor areas [22,27,37,48,55,61–65], striatum [22] and hippocampus [28,40,45,52,66–69]. Comparing the variability of neuronal feature selectively therefore is challenging—nevertheless, we would first like to provide an update on long-term neuronal variability assessments (for a previous in-depth review see [16]; for a review on short-term trial-to-trial variabiliy see [70]).…”

A robot for high yield electrophysiology and morphology of single neurons in vivo

“…Increased spiking (Fig. 4a2) was observed in this cell post-electroporation25262833. After a 4-day expression, we successfully recovered this neuron's pyramidal morphology at matching location and depth.…”