1. Modulatory Influence of Auditory Cortex on the Activity of Medial Geniculate Body Neurons in Rat R. Moucha1, J. Poeplar2, D. Suta2, M.P. Kilgard1, J. Syka2 1 School of Behavioral and Brain Sciences, University of Texas at Dallas, USA 2 Institute of Experimental Medicine ASCR, Prague, Czech Republic

2. ABSTRACT
Cortico-thalamic feedback projections greatly outnumber the ascending thalamo-cortical input fibers, yet there is little understanding of the functional role of these connections. The purpose of this study was to investigate cortico-thalamic modulation in the rat (Long-Evans strain) auditory system. We examined the effects of electrical activation of the deep layers of the auditory cortex on the responses of neurons located in the medial geniculate body (MGB). Extracellular multiunit recordings were collected in the MGB with 16 channel multielectrodes during simultaneous electrical stimulation of the auditory cortex (short train of monophasic pulses, µA). Neuronal responses were evaluated and compared during acoustic stimulation (AS) with broadband noise, electrical stimulation (ES) and paired acoustic and electrical activation (AS+ES). Broadband noise evoked excitatory sustained activation with an increased onset in the majority of MGB sites. This response was mostly suppressed after AS+ES pairing when the delay between ES and AS was between 10 and 30ms and the suppression declined at longer intervals. In most cases the suppression affected the late part of the response.
ES alone evoked short latency excitation within 5ms and a longer lasting suppression of spontaneous activity. In some neurons the suppression of spontaneous activity decreased over repetitions of stimulation. At some MGB sites ES triggered late excitatory responses at approximately 200 ms. The relationship between the location of electrical stimulation and its effect on different parts of the MGB are also being examined.
This research was supported by GACR grant 309/04/1074.

3. AIM OF THE STUDY To investigate the modulatory effects of
cortico-thalamic feedback projections
MGB receives extensive feedback from cortical layer VI
These projection greatly outnumber the ascending fibers from thalamus to the cortex.
Direct cortical feedback projections to MGB are excitatory. IV V VI +
MGB
RTN _
An important question to answer is how this feedback participates in the specific processing of sensory information

4. METHODS |||| |||| // 1-2 Tungsten stimulating electrode in A1
Recording
electrode ES AS
||||
|||| //
time (ms)
delay
1-2 Tungsten stimulating electrode in A1
Michigan 16 ch recording electrode in MGB
Acoustic stimulus = Broadband Noise 50ms duration (AS)
Electrical stimulus = 4 monophasic pulses .33ms width, 500Hz (ES)
Stimulation = AS alone, AS+ES, ES alone
Current = 12.5, 25, 50, 100A , monopolar
Delay = 10, 30, 60, 90, 120, 180, 240ms
Peristimulus Recording = 400 ms
1set = 100 repeats of one stimulation per 800ms (0.8 Hz)
Tracts between 5-6 mm post to Bregma,   depth

5. Excitatory Effect of Cortical ES on Thalamic Responses
during ES alone (dotted) and ES+AS (solid)
Position of stimulating electrode in A1,
and MGB recording 4000  depths
el.
pulse
Excit. to AS ES
||||
30ms
Time (ms)
ES+AS p D A V
Recordings of thalamus action potentials
ES elicits short latency (~3-4ms) excitatory responses in MGB
In 60% of the units recorded

6. Effect of Electrical Stimulation1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
MGB
RR12, T5, rec
Total recordings:
N = 10 rats, under ketamine anesthesia
Sites = 384 multiunit recordings from auditory responsive thalamic sites
Tracts = 24 (16 tracts in MGv, 5 tracts in MGd, 3 tracts in VPM)
Yield = channels on each tract

7. Effect of Cortical BF of Stimulated Site
??, ??, , , , , , , , , , , , , ,
Suppression in ch 1-12, BF’s < 7 kHz (cortical BF = 7 kHz)
Less/no suppression in ch 13-16, BF’s > 7 kHz
All channels are suppressed by ES alone
Ch/CF: 1/?, 2/?, 3/4, 4/3, 5/4, 6/5, 7/4, 8/5, 9/4, 10/6, 11/7, 12/6,
13/9, 14/12, 15/14, 16/15

8. Immediate Recovery from Suppression
RR12, T4, rec

9. Ch 9
Ch 13
Rr14, rec.4-5-6, ES50uA

10. Effect of Stimulating Current IntensityAS
AS+ES_12.5 A
AS+ES_25 A
AS+ES_50 A
Group data rr12, rr13, 3 different tracts, n= 48 sites
N = 48 sites

11. Late evoked excitation, “rebound” from strong inhibitionAS
AS+ES_25 A
AS+ES_50 A
In some units stronger ES currents in addition to increasing
suppression also evoked a late excitatory response
@ 200 ms from ES onset

12. Effect of Delay between ES and AS : 30, 90, 180 ms
N = 64 sites
30ms
90ms

13. Responses to AS at increasing delays between AS and ES
Mean response of 16 channels from one MGB tract
Difference in mean spikes evoked over 70 ms from the response onset
Delay –30 ms indicates reversed order between ES and AS
(i.e. AS precedes ES by 30ms)

14. Types of MGB responses to AS, in 3 units from the same tract
Onset only (37%) On + Off (15%) Onset & sustained (48%)
RR18
Stability over time: dotted line is response to AS (broadband noise 50ms) after 30 min, shifted

15. Raster plots of Responses from 3 units to 100 reps of AS, and AS+ES
PSTH’s of the Responses presented above during AS and AS+ES

16. Effect of Cortical Blockade by Muscimol on MGB Responses
Pre Musc AS
AS+ES
Post 30 min AS
AS+ES
No effect of ES during cortical inactivation
(i.e. no suppression of AS response during cortical stimulation under Muscimol)
Late responses are abolished
Response latency is increased
Pre Muscimol
Post 10 min
Post 30 min
Post 1hr
Post 2 hrs
RR18,

17. CONCLUSIONS
Electrical activation of A1 suppresses the response of
MGB neurons to subsequent acoustic stimuli delivered
within 30 ms after ES, and facilitates the responses at
delays greater than 90 ms.
The magnitude of suppression increases with the
intensity of stimulating current
(more suppression if more current).
There is no lasting effect of electrical stimulation,
MGB responses recover to baseline immediately after A1
stimulation stops.