Scientists discuss technological advancements and present novel application of new head-mounted and implantable, wireless sensors for neural recording and stimulation in freely moving animals.

Wireless Recording and Stimulation Technologies for in vivo Electrophysiology in Conscious, Freely Behaving Rodents

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Monitoring Auditory Cortex Plasticity With a TBSI Wireless Recording System

Dan Sanes, Ph.D.ProfessorCenter for Neural ScienceNew York University

Melissa Caras, Ph.D.Postdoctoral Fellow

Center for Neural ScienceNew York University

Do auditory cortex neurons adjust their sensitivity to sound?

Perceptual learning

Developmental hearing loss

Amplitude modulation depth

200 msAm

plit

ude

Threshold: smallest depth detected

unmodulated

0 dB

-3 dB

-6 dB

-9 dB

-12 dB

Human auditory perceptual learning

Fitzgerald and Wright, 2011

PostPre

Group

-12

-10

-8

2Pre-

test

4 6 Post-

test

3 5 7

AM

depth

thre

shold

(dB

re

: 1

00

%)

Day

-14

Individual subject

Good

Bad

Heffner and Heffner, 2007

Gerbil audiogram is similar to human

.125 1 2 4 8 16 32

Frequency (kHz)

.5

Threshold

(dB SPL)

-20

0

20

40

60

80

.032

Human

Gerbil

Time (sec)

Training on an AM detection task

Safe

Correct reject

Safe

False alarm

Warn

Hit

Warn

Miss

d’ = z(hit rate) - z(false alarm rate)

Amplitude modulation (AM) detection

Chronic electrode implants

Surgical Approach

Rostral

Caudal

Lambda

Craniotomy site

Rostral

Caudal

Lambda

Surgical Approach

Rostral

Caudal

Surgical Approach

Rostral

Caudal

Surgical Approach

Rostral

Caudal

Surgical Approach

Rostral

Caudal

Surgical Approach

Chronic electrode implants

neural d’ = z(Firing rateWarn) – z(Firing rateSafe)

TDT RZ5

TDT TB32

TBSI Receiver

TBSI Headstage

Wireless recording from auditory cortex

d’

AM depth (dB re: 100%)

-100 -1 0

4

3

2

1

Individual psychometric function

-10

Behavioral AM detection threshold

Neural response0 dB

-3 dB

-6 dB

-9 dB

-12 dB

Unmod

100 sp/s

time (sec)0 1AM depth (dB re: 100%)

-100 -1 0

4

3

2

1

Single neurometric function

d’

-10

AM processing during task performance

d’

AM depth (dB re: 100%)

-100 -1 0

AM depth (dB re: 100%)

-100 -1 0

4

3

2

1

4

3

2

1

Single neurometric function

-10 -10

Compare behavioral & neural thresholds

Individual psychometric function

Training improves behavioral and neural sensitivity

4

3

2

1

0

d’

0-10-20

AM depth (dB)

4

3

2

1

0

d’

AM depth (dB)

0-10-20

Behavior Multiunit

Caras and Sanes, PNAS 2017

mean +/- SEM

AM detectionthreshold (dB)

poor

good

-6

-10

-2

-14

1 2 3 4 5 6 7

Day of training

Caras and Sanes, PNAS 2017

-18

Training improves behavioral and neural sensitivity

Engaged PostPre

Measuring a top-down mechanism

AC ACAC

top-down

auditory cortex

bottom-up

AC AC

EngagedPre Post

AM sensitivity is enhanced

Caras and Sanes, PNAS 2017

250 ms

100 Hz

Engaged

Pre

Post

Evidence for enhanced top-down process

mean +/- SEM

AM detectionthreshold (dB)

poor

good

-4

-6

-8

-10

-12

-2

-14

1 2 3 4 5 6 7Day of training

Behavior

Caras and Sanes, PNAS 2017

Perceptual learning

Developmental hearing loss

Do auditory cortex neurons adjust their sensitivity to sound?

Amplitude modulation rate discrimination

GoAM rates >4 Hz

NogoAM rate of 4 Hz

Perceptual and neural sensitivity

Go trials (>4 Hz) Nogo trials (4 Hz)

Sexual

maturation

Hearing

onset

Permanent conductive loss

malleus

removal

Developmental hearing loss

4 HzNogo

Behavioral measure of AM discrimination

Control behaviorHearing loss behavior

Population data: Psychometric performance

von Trapp, unpublished

AM rate (Hz)

10 20 3053

d’

3

4

2

1

0

good

poor

Control (n=289 neurons)

Hearing loss (n=280 neurons)

Neurometric functions

Population data: Neurometric performance

AM rate (Hz)

10 20 3053

d’

3

4

2

1

0

von Trapp, unpublished

Psychometric performance

Effect of task engagement

Engaged in task Disengaged(hear sounds presented during task engagement)

AM rate (Hz)

10 20 3053

d’

3

4

2

1

0

Sensitivity emerges during task performance

Control(n=289 neurons)

Hearing loss(n=280 neurons)

disengaged (same stimuli)

engaged in task

Gardiner von Trapp, unpublished

Neurometric functions: Control vs CHL

4 Hz

Nogo

AM rate (Hz)

10 20 3053

d’

3

4

2

1

0

Engaged vs disengaged sensitivity

smaller enhancement during task engagement

Control(n=289 neurons)

Hearing loss(n=280 neurons)Gardiner von Trapp, unpublished

4 Hz

Nogo

Sensitivity emerges during task performance

Summary

• TBSI headstage permits real-time assessment of cortical sensitivity in freely moving animals

• Perceptual learning is associated with modulation of top-down signaling to auditory cortex

• Following a period of developmental hearing loss top-down signaling becomes weaker

Products Designed for Research

Our goal is to accommodate your neural interface equipment

needs, from electrodes to data digitization and analysis. All of our

products are designed to aid with in-vivo neuroscience research,

especially in the fields of electrophysiology, psychology, neurology,

and pharmacology, as well as disease origin studies.

To learn more about our biointerfacing solutions, visit www.trianglebiosystems.com

TRIANGLE BIOSYSTEMS INTERNATIONALA Division of Harvard Bioscience

IMPLANTABLE DEVICES for NEUROMODULATION of GASTROINTESTINAL FUNCTION

Bradley BarthPh.D. CandidateShen LaboratoryDuke University

SHEN LAB: CONTROL SYSTEMS in the GUT

FUNCTIONAL GASTROINTESTINAL DISORDERS

Sebastian Kaulitzki

• 1 in 5 people are diagnosed with FGID

• Diagnosis is based on patient symptoms

• Symptoms can be severe and debilitating

• Associated with long term damage to ENS

ENTERIC NERVOUS SYSTEM

Furness and Costa (1980)

EMG RECORDINGS in AWAKE RATS

Motivation:

• Gut motility is dramatically affected by

anesthesia

• Physiologically-relevant events are best

captured in awake animals

EMG Recording Features:

• Wireless

• Fully implantable

• Multi - channel

Methods:

• Implant 5ch recording device in rats

• Record EMG activity from hind legs in awake rat

• Evoke leg twitch response to test device

DEVICE and ELECTRODE IMPLANTATION

CAGE and RAT CONFIGURATION

TBSI 5ch Receiverwith Channel Lock LED on

TBSI 5ch ReceiverReceiver antennas

Inductive Powered Cage Collar

CAGE and RAT CONFIGURATION

RECORDED EMG TEST DATA from RAT

EMG RECORDING

SACRAL NERVE STIMULATION in AWAKE MICE

Motivation:

• Sacral nerve stimulation is an FDA-approved therapy for treating motility disorders

• Therapy stimulates sacral nerve in awake patients

Nerve Stimulator Features:

• Wireless

• Fully implantable

• Multi - channel

Methods:

• Implant 3ch stimulation device in mice

• Find motor threshold in non-survival implant

• Demonstrate nerve stimulation in awake mice

MOUSE SACRAL NERVE STIMULATION

ACUTE SACRAL NERVE STIMULATION

IMPLANTABLE STIMULATOR SURGERY

AWAKE SACRAL NERVE STIMULATION

SUMMARY

Demonstrated fully implantable and wireless devices for:

• 5 channel EMG recording in awake, freely moving rats

• 3 channel nerve stimulation in awake, freely moving mice

Dan Sanes, Ph.D.ProfessorCenter for Neural ScienceNew York University

Bradley BarthPh.D. CandidateShen LaboratoryDuke University

Melissa Caras, Ph.D.Postdoctoral FellowCenter for Neural ScienceNew York University

Thank You

Continue the discussion at Society for

Neuroscience

BOOTH 1522

For additional information on the products and applications presented during this webinar please visit www.trianglebiosystems.com

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