Sample Projects

Go back to:

Overview

Research publications

Here are some projects we have completed recently. More projects can be found at my colleagues’ website (tadpole research at Bristol).

Intrinsic properties enable motor program switches (Li 2015, J Neurosci)

Many neural circuits are capable of producing multiple, patterned outputs. This is because the synaptic connections among some network neurons are “ubiquitous” but susceptible to fast reconfiguration when sensory inputs or neuromodulatory states change. In this study, I have identified that certain ion channels in the tadpole motor circuit can quickly shift neuronal firing thresholds depending on network excitation levels. Neuron-type specific expression of the channels then allows selective recruitment/depression of different neurons, dynamic configuration of the circuit and potential switching between motor programmes (swimming and struggling in tadpoles).

Self-absorbed comments: In line with many invertebrate studies, this work shows that functional circuits can be very different from the synaptic connection maps. Also, it implies “ubiquitous” synaptic connections may be necessary for multiple functional networks.

A.The firing thresholds (numerals with arrows) of an inhibitory interneuron (aIN) are raised by hyperpolarised membrane potentials. B.  Thresholds of an excitatory interneuron (dIN) are lowered by hyperpolarisation. I is the current injection used to alter membrane potential and evoke firing. RMP is the resting membrane potential.

A. The firing thresholds (numerals with arrows) of an inhibitory interneuron (aIN) are raised by hyperpolarised membrane potentials. B. Thresholds of an excitatory interneuron (dIN) are lowered by hyperpolarisation. I is the current injection used to alter membrane potential and evoke firing. RMP is the resting membrane potential.

The same neural circuit generates two rhythms (Li et al 2014, J Neurosci). Antiphase oscillations and synchrony are arguably the two most common neural rhythms in the CNS. We have found that both rhythms are intrinsically embedded in the same tadpole swimming circuit, which comprises of two half-centres coupled by reciprocal inhibition. The antiphase swimming rhythm is the stable output in normal conditions. Modelling predicts that synchrony can be converted to a stable regime by delaying the arrival of inhibition between the half-centres.

Self-absorbed comments: This research shows that the same central pattern generator based on post-inhibitory rebound can generate two different rhythms without circuit reconfiguration.

A. A commissural interneuron is recorded simultaneously with motor nerve activity from the opposite side. Red traces illustrate a brief bout of synchrony when the left and right activities appear in phase (c.f. out of phase activity after the bout). B. In a computer model built for tadpole swimming, synchrony (red traces) can be toggled on and off by injecting brief step currents into dINs.

A. A commissural interneuron is recorded simultaneously with motor nerve activity from the opposite side. Red traces illustrate a brief bout of synchrony when the left and right activities appear in phase (c.f. out of phase activity after the bout). B. In a computer model built for tadpole swimming, synchrony (red traces) can be toggled on and off by injecting brief step currents into dINs.

Normal tadpole swimming operates on rebound from reciprocal inhibition (Moult et al., 2013, Neuron). We wanted to identify which mechanism, rebound or pace-maker firing, dominates normal swimming activity. Using two fast silencing methods (optogenetics and large –DC injections into dINs, see other projects), we found that tadpole spinal activity on one side is dependent on the other side being active. Analyses show:
• the failure of activity result from depression of reciprocal inhibition
• pace-maker driven swimming-like rhythms requires a recovery period

Self-absorbed comments: This work lends strong support to the critical role for reciprocal inhibition in locomotor control proposed by Graham Brown (Brown’s hypothesis, Brown 1911, 1914).

A shows a tadpole expressing GFP-tagged ArCh constructs, an inhibitory reverse proton pump that can activated by yellow lights at 580 nm. ArCh was only expressed on the right hand side. B shows yellow light quickly switches off swimming monitored from the left hand motor nerve in an intensity-dependent manner. 1-10 are consecutive trials with or without light.

A shows a tadpole expressing GFP-tagged ArCh constructs, an inhibitory reverse proton pump that can activated by yellow lights at 580 nm. ArCh was only expressed on the right hand side. B shows yellow light quickly switches off swimming monitored from the left hand motor nerve in an intensity-dependent manner. 1-10 are consecutive trials with or without light.

The control of tadpole swimming frequency by excitation and inhibition (Li & Moult 2012, J Neurosci). Tadpole swimming rhythms are maintained either from rebound or pace-maker firing in the excitatory interneurons, dINs. By analysing how excitation and inhibition affect dIN rebound firing speed, we have identified that:
• Background excitation directly determines swimming frequency
• Strong phasic inhibition in certain cases can speed up swimming

Self-absorbed comments: It is rare in vertebrate central nervous system that changing the activity of single neurons can affect behavior. Fortuitously, single dIN firing can affect swimming. This makes testing many aspects of tadpole swimming control straightforward.

Injecting large –DC into a single dIN (blue traces and symbols) instantly reduces swimming frequency monitored from motor nerve bursts (m.n.).

Injecting large –DC into a single dIN (blue traces and symbols) instantly reduces swimming frequency monitored from motor nerve bursts (m.n.).

Identification of neurons that fire first in a behavior (Soffe et al., 2009, J Physiol). The neurons that fire first during certain behaviour can imply their critical, driving roles. Using loose-patch recordings, we recorded many neurons from single tadpoles. Analyses show that the earliest-firing neurons during a swimming cycle are the excitatory interneurons (dINs), located in the caudal hindbrain and rostral spinal cord region. While dIN EPSPs could directly drive the activity of other neurons, dIN firing itself appeared to rely on reciprocal inhibition (rebound).

Self-absorbed comments: It is uncommon to be able to find the neurons that fire first in a function mediated by the central nervous system. Though the approach we have used here is not ideal, the results are clear. The properties of dINs thus potentially hold many keys to swimming control.

A.Tadpole central nervous system (grey) with segmented swimming muscles. B. Relative timing of neuronal firing during a swimming cycle. Each red dot is averaged timing for a dIN. Black dots are for other types of neurons. Negative time means firing before motor nerve bursts (0 ms). Distance starts from midbrain (0 mm).

A.Tadpole central nervous system (grey) with segmented swimming muscles. B. Relative timing of neuronal firing during a swimming cycle. Each red dot is averaged timing for a dIN. Black dots are for other types of neurons. Negative time means firing before motor nerve bursts (0 ms). Distance starts from midbrain (0 mm).

11 Responses to Sample Projects

  1. Barry says:

    I am truly grateful to the osner of this web page who has share this fantastic article at
    here.

  2. I quite like looking through a post that can make men and
    women think. Also, many thanks for permitting me
    to comment!

  3. Taylor says:

    I read this post fully regarding the difference of hottest and previous
    technologies, it’s remarkable article.

  4. Margarito says:

    I am noot sjre the place you’re getting your info, but great topic.

    I musst spend some time studying much more or understanding more.
    Thank you for wonderful info I was in search of this info for my mission.

  5. Flora says:

    My relawtives always say that I am killing myy time here at web, but
    I know I am getting familiarity every day by reading thes pleasant articles or reviews.

  6. Impact Video says:

    The above comments do look a little strange to me. How come they have been posted?

  7. Pumpkin Photography Studio is a fully equipped versatile photography studio available for hire photographers, videographers, students and professionals.

  8. Manchester says:

    Please take our survey.

  9. Here at Johns services we provide a comprehensive service

  10. Would you take a moment to visit our new interactive website created with co-operation with Manchester University.

  11. Tadpoles are a wonderful little creature.

Leave a Reply

Your email address will not be published.